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Phospholipase A2 (PLA2) has been suggested to be present in herniated disc tissue and it could possibly be involved in sciatica/ discogenic back pain mechanisms. In the present study the occurrence of two different phospholipase A2 enzymes, (1) low molecular weight (14 kDa) group II synovial-type (sPLA2) and (2) high molecular weight (85 kDa) group IV cytosolic (cPLA2), were compared. Fifty-three disc prolapses obtained at disc operations were analyzed by immunohistochemistry, using anti-human monoclonal antibodies to sPLA2 and cPLA2, respectively. Only cell-associated (disc cells, hyaline cartilage chondrocytes) sPLA2 and cPLA2 immunoreactivity could be observed. The results showed that sPLA2 was more common (25/53, 47%) than cPLA2 (13/53, 25%). sPLA2 and cPLA2 were simultaneously present in 13 of 53 samples (25%). However, both PLA2 enzymes were predominantly present in hyaline cartilage cells (sPLA2: 16/53, cPLA2: 5/53), being less commonly observed in disc cells (sPLA2: 6/53, cPLA2: 3/53). In addition, three samples for sPLA2 and two samples for cPLA2 exhibited immunoreactivity in cartilage and disc cells simultaneously. sPLA2 was observed in no other locations, but in 3 of 53 samples cPLA2 was observed more diffusely in areas of granulation tissue, possibly in macrophages. No gender- or age-related dependence for either type of PLA2 enzyme immunoreactivity could be observed. Neither did their occurrence relate to clinical data such as straight leg raising or neurological deficit. The results do not support a major role for either of the two disc-cell-associated PLA2s in disc pathophysiology. For both enzymes, the major pool appears to reside in cartilage tissue cells, presumably in dislodged end-plate fragments. Disc cells are apparently unlikely candidates for major PLA2 storage. [ABSTRACT FROM AUTHOR]

Angiogenesis is essential in tissue growth and regeneration. There are several factors that are able to stimulate vascular endothelial cell growth, including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Disc herniation tissue (DHT) contains vascular ingrowth, which promotes granulation tissue formation. In this study we observed 50 disc herniations for PDGF and VEGF immunoreactivity. PDGF immunopositivity was detected in 38 samples (78%). In 28 samples (56%) there were PDGF immunopositive capillaries, PDGF immunopositive disc cells were detected in 19 samples (38%) and PDGF immunopositive fibroblasts in 6 DHT samples (12%). VEGF immunopositive capillaries were identified in 44 DHT samples (88%). For neither growth factor was immunopositivity dependent on preoperative radicular pain duration. In extrusions (n = 25) VEGF immunopositive capillaries were detected in 23 samples (92%) and PDGF immunopositivity in 21 samples (84%). PDGF immunopositivity was more commonly associated with capillaries than with nuclei of disc cells. In sequesters (n = 20) VEGF immunopositive capillaries were identified in all samples and PDGF immunopositivity in 16 (80%). As in extrusions, PDGF immunoreaction was more prevalent in capillaries than in disc cells. Patient age did not relate to VEGF expression. In all age groups it was higher than 80%. Thus capillaries in disc herniation tissue are evidently newly formed and our results demonstrate that PDGF and VEGF participate in the neovascularization process. The presence of PDGF in fibroblasts and in disc cells suggests that this growth factor regulates the function of these cells, possibly the proliferation of the cells and the production of extracellular matrix components. [ABSTRACT FROM AUTHOR]

Twenty disc herniations (DH) were studied immunocytochemically for macrophages and blood vessels. Serial thin frozen sections were immunostained with an antibody specific for tissue macrophages (monoclonal antibody to CD68 antigen) and the endothelium of blood vessels (polyclonal antibody to von Willebrand factor). With this method, blood vessels, often abundant, were observed in as many as 16/20 (80%) of the DH studied, 12 disc extrusions and 8 sequestrated discs, whereas abundant macrophages were noted in 11/20 (55%) of the DH. Macrophages were present only in areas with blood vessels and had presumably infiltrated the tissue from them. As has been noted previously, some blood vessels are apparently newly formed as a result of tissue injury, whereas others were present in the disc prior to herniation. This is suggested by the lack of a clear correlation between the presence or absence of blood vessels and the preoperative duration of radicular pain. In areas of the DH where cartilage fragments occurred, both macrophages and blood vessels were particularly abundant. [ABSTRACT FROM AUTHOR]

There is increasing evidence that-back pain may originate from degenerated or damaged disks, even in the absence of disk herniation. For a study of the pattern of innervation in injured disks, the anterior part of the annulus fibrosus of a lumbar disk in 11 domestic pigs was incised with a scalpel through a retroperitoneal approach. The animals were killed 2 weeks, 1, 2, 3, and 5 months postoperatively, and the whole anterior annulus of each injured disk and corresponding tissue from intact animals were excised. Cryostat sections 20 microns thick were cut from the surface downward, fixed, and stained with different antisera. Antisera to neurofilament triplet protein (R39), protein gene product (PGP) 9.5 and synaptophysin were used as general neural markers. Antiserum to substance P (SP) and calcitonin gene-related peptide (CGRP) were used to localize nerves mainly of the sensory type, and C flanking peptide of neuropeptide Y (CPON) to visualize nerve fibers of the sympathetic type. It was observed that in the intact porcine disk, the outer and middle parts of the anterior annulus were innervated to a depth of 7 mm from the annular surface, but the innermost annular layers showed no immunoreactivity to any of the neural antibodies. Disk injury did not cause any major changes in the nerve topography of the wound area, even though there were granulation tissue and neovascularization in this area. [ABSTRACT FROM AUTHOR]

Introduction: This prospective magnetic resonance imaging (MRI) study in chronic low-back pain (CLBP) patients evaluated the natural course of degenerative lumbar spine changes in relation to Modic 1 type changes (M1) within 1 year.Materials and Methods: From 3,811 consecutive CLBP patients referred to lumbar spine MRI 54 patients with a large M1 were selected using strict exclusion criteria to exclude specific back disorders. Follow-up MRI was obtained within 11-18 months.Results: At baseline M1 was associated with an adjacent endplate lesion in 96% of the cases. In follow-up, an unstable M1 was associated both with an increase of endplate lesions, decrease of disc height and change in disc signal intensity, most found at L4/5 or L5/S1. In disc spaces without M1, progression of degenerative changes was rare.Conclusion: Endplate deformation, decreasing disc height and change of disc signal intensity appear essential features of accelerated degenerative process associated with M1. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of cold treatment to limit edema, decrease pain, and induce effective muscle relaxation in soft tissue injuries is widespread. PURPOSE: To compare the efficacy of a novel cold gel with that of a placebo gel in patients with a soft tissue injury. STUDY DESIGN: Prospective randomized double-blinded controlled study. METHODS: Seventy-four patients with sports-related soft tissue injury were randomly assigned to active cold gel (Ice Power) or placebo gel groups. The gel was applied four times daily on the skin for 14 days. Clinical assessment was made after 7, 14, and 28 days with use of visual analog scale ratings. RESULTS: Pain scores decreased from 59 to 30 during the first week, to 14 by the second, and to 7 by the end of study in the cold gel group. In the placebo group, pain scores decreased from 58 to 45, 26, and 13, respectively (significant difference). Patient satisfaction with treatment was 71 in the cold gel group and 44 in the placebo group (significant difference). Disability decreased significantly more rapidly in the cold gel group. CONCLUSIONS: Cold gel therapy provided an effective and safe treatment for sports-related soft tissue injuries. [ABSTRACT FROM AUTHOR]

Ingrowth of nerves and blood vessels is regarded as a part of disc degeneration. Schwann cells, which guide the development and regeneration of nerves both in the central and peripheral nervous system, have recently been located in degenerated human discs. The purpose of this study was to investigate by immunohistochemical methods, whether or not there was nerve, Schwann cell and blood vessel ingrowth in experimentally induced acute (3 weeks) and subacute (3 months) annular tears; and to study the detailed topography of such nerve ingrowth when present. Ingrowth of nerves and Schwann cells has so far not been studied in experimentally induced acute annular tears. A stab incision with a scalpel blade was made in two adjacent lumbar discs in adult sheep (n = 9). The L2-L3 discs were injured superficially, whereas in L3-L4 discs the incision reached the nucleus pulposus (full-thickness injury). The animals were sacrificed three weeks (acute injury, n = 3) or three months (subacute injury, n = 6) post-operatively. Discs were immunoassayed for general neuronal markers (protein gene product 9.5, PGP 9.5 and synaptophysin, SYN), Schwann cell marker (glial fibrillary acidic protein, GFAP) and endothelial marker (CD 31). Nerves visualized with all antibodies employed were situated inside the injured area and mainly near and around blood vessels although free nerve endings could be seen also. PGP 9.5-immunopositive nerves were evident in every sample. Immunoreactivity to SYN and GFAP was not observed in control discs. Such immunoreactivity appeared already at 3 weeks(acute injury) in a few samples, and was present in all samples at 3 months (subacute injury). For the superficial injury, nerves did not penetrate deeper than in control discs until at 3 months. With more extensive annular injury, mean values for both nerve and Schwann cell penetration were higher. Blood capillaries were visible deeper in the inner annulus than neural tissues immunopositive to PGP 9.5, GFAP... [ABSTRACT FROM AUTHOR]

Stepwise distraction of the rabbit tibia after a transverse diaphyseal osteotomy was performed in an external fixator. The goal was to clarify the fine-structural parameters of long-bone lengthening. The tibias were vertically cut and studied 5 weeks after the osteotomy, and the specimens with an initial gap without further lengthening were compared with those with a gap and stepwise distraction. The role of periosteal bone induction was essential for the ossification of a growing gap, whereas the ossification of a simple gap proceeded equally by the endosteal and periosteal routes. The distraction resulted in vertical organization of the premature callus tissue at the proximal pole of the distracted gap, while the distal part of the gap area was deficiently filled by endosteal bone but preliminarily fixed by a bridge of periosteal callus tissue. [ABSTRACT FROM AUTHOR]

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During a follow-up period of 16 weeks in 18 pigs, macroscopical and histological studies revealed inva sion of fibroblasts and mesenchymal cells around the carbon fiber prosthesis inserted to replace the ACL but scarce tissue ingrowth into the prosthesis proper. There was no adherence of the carbon ligament onto the bony channels. The peak tensile strength of the reconstructed ligament was about one third of the paired normal ACL ligament during the 16 week exper iment. [ABSTRACT FROM PUBLISHER]

Thirty-three patients fulfilling the diagnostic criteria for primary fibromyalgia completed an eight-week double-blind treatment trial with the drug zopiclone. Of outcome measures studied a score expressing subjective sleep quality showed improvement in more than ninety percent of zopiclone patients at 4 weeks and nearly eighty percent at 8 weeks, but similar improvement was also reported by more than sixty percent of the patients on placebo. Patient self-assessment of a treatment effect also showed an advantage for zopiclone, with most patients in the placebo group considering their state as unchanged at 8 weeks. According to examiner assessment, however, half the patients in both groups showed improvement at 8 weeks. For other assessment variables, e.g. dolorimeter assessment of widespread tenderness, visual analogue scales and pain drawings for pain and other subjective feelings of discomfort, the effects of zopiclone treatment were at the same level as those of placebo. [ABSTRACT FROM AUTHOR]

Glomus (Type I) cells of the carotid body of adult rats were studied electron microscopically after fixation with potassium permanganate or with glutaraldehyde and osmium tetroxide. Two permanganate fixation methods (using Krebs-Ringer-glucose, pH 7.0, or acetate buffer, pH 5.0) were compared. Numerous dense-cored vesicles were observed only in about one tenth of the glomus cells when neutral permanganate was used for fixation, although all glomus cells showed such vesicles after fixation with glutaraldehyde and osmium tetroxide. Numerous vesicles with a dense core were observed in about one third of the cells after fixation with acid potassium permanganate. With this fixation, small dense-cored vesicles similar to those in adrenergic nerve terminals were occasionally seen in the cytoplasm of glomus cells. It is tentatively concluded that the amine-storing vesicles of the carotid body are different from those in the small intensely fluorescent (SIF) cells and those in adrenergic nerve terminals. [ABSTRACT FROM AUTHOR]

Mast cells in labial salivary glands obtained from patients with xerostomia with or without focal sialadenitis/Sjögren's syndrome were studied. There was no significant correlation between the intensity of local lymphocyte infiltration and the morphometrically analysed number of mast cells staining positive with toluidine blue. Histamine staining with heterologous 11C antiserum showed significantly fewer positive cells than staining with toluidine blue (mean (SD) 62 (10) v 138 (30)). This suggests heterogeneity of the mast cell population. Furthermore, there was a correlation between the focus score and the number of mast cells containing histamine. This suggests that the proliferation of mast cells containing histamine may be locally regulated by the immune inflammation, possibly through mediators from macrophages and fibroblasts. In contrast, the number of mast cells staining positive with toluidine blue could not be used as a marker of the degree of local inflammation. Although transmission electron microscopic analysis did not disclose signs of 'en masse' mast cell degranulation, mast cells may have a role in the local disease process. [ABSTRACT FROM PUBLISHER]

Type A synovial lining cells have been shown to contain lysozyme in their lysosomes. This might be phagocytosed because synovial fluid contains lysozyme originating from tissue macrophages and articular cartilage but in arthritides, in particular, from neutrophils. In situ hybridisation with 35S labelled cDNA was used to detect mRNA for lysozyme over synovial lining in patients with rheumatoid arthritis. No hybridisation was found with lactoferrin cDNA, which was used as a negative control. Computer search against the EMBL gene bank (release 14) did not show any significant cross hybridisation to a known sequence. In cytological specimens 35S-cDNA:mRNA hybrids were observed in positive but not in negative control cells. The presence of lysozyme and its mRNA suggests that type A synovial lining cells are of mononuclear phagocyte lineage. [ABSTRACT FROM PUBLISHER]

Extensive secretion by exocytosis was demonstrated in the glomus (type I) cells of the adult rat after perfusion of carotid bodies with a potassium-rich (high K) glutaraldehyde fixative. Similar secretory profiles were very rare with a glutaraldehyde fixative containing a low concentration of potassium (low K). The increase in the incidence of exocytotic profiles in glomus cells with the high K fixative was highly significant, whereas no statistical difference could be observed in the incidence of coated pits with the different fixatives. Exocytotic profiles were characterized by the following features: (1) they predominated in non-synaptic regions, but were occasionally observed near synapses between two glomus cells; they were not observed near synapses between glomus cells and nerve terminals; (2) extruded electron-dense material associated with coating of the cell membrane was frequent; (3) different stages of dissolution of the extruded granule material was evident. The possible role of exocytosis as a mode of secretion in the glomus cells and the characteristics of the new high K-glutaraldehyde fixative are discussed. [ABSTRACT FROM AUTHOR]

Glomus cells from carotid bodies of adult rats dissociated by means of collagenase or collagenase + trypsin were used to study by electron microscopy the endocytotic uptake of cationized ferritin (CF) tracer into subcellular compartments. The glomus cells were incubated with the tracer (1) in a basic salt medium (BM), or (2) in the BM into which calcium ionophore A23187 had been added, or (3) in a potassium-rich medium. Incubation of the cells in BM containing CF for 30 min resulted in attachment of the tracer to the cell membrane and uptake of a few solitary tracer particles into small vesicles and multivesicular bodies. No uptake into the cisternae of the Golgi apparatus was observed. Further incubation in BM containing CF for another 30 min resulted in increased uptake of the tracer into small vesicles and multivesicular bodies. A similar pattern of uptake was observed when the dissociated glomus cells were first preincubated in BM with CF for 30 min and then incubated for 1 min or 30 min in the BM solution containing both the ionophore and CF. Upon such incubation, CF particles were seen to penetrate into coated pits and sites of exocytosis at the cell surface. When the 30-min preincubation in BM was followed by incubation in a CF-containing potassium-rich medium for 15-30 min, uptake into vesicles, small lysosomes and occasionally also into profiles of the smooth endoplasmic reticulum was seen. Endocytotic mechanisms of the glomus cells are outlined. [ABSTRACT FROM AUTHOR]

An attempt was made to study the subcellular localization of calcium in carotid body glomus cells of adult rats using fixation with glutaraldehyde followed by treatment with a mixture of pyroantimonate and osmium tetroxide. Precipitates were seen as electron-dense particles (EDP) in the glomus cells, mostly within membrane-bound organelles, such as dense-cored vesicles, mitochondria, small clear vesicles, multivesicular bodies, and especially in lysosomes. However, EDP were also seen in the nuclei and in the free cytoplasm of the glomus cells and even outside them. Preincubation of carotid bodies in media containing calcium and either high potassium or calcium-ionophore A 23187 resulted in a marked increase in the general precipitation pattern, there being an increased amount of EDP both in the glomus cell nuclei and in the cytoplasm. Dense-cored vesicles more often showed precipitates than those in the controls. Some dense-cored vesicles contained multiple precipitates, typically located in the electron-lucent area between core and vesicle membrane. Extensive diffusion of ions probably occurred during fixation before precipitation, making the localization of calcium and other precipitating cations unreliable. However, it is possible that precipitates, which were regularly seen in the dense-cored vesicles, may reflect the content of bound calcium. The possible significance of calcium in glomus cell function is discussed, and the need for more adequate methods is emphasized. [ABSTRACT FROM AUTHOR]

Recent animal studies indicate that vasopressin has analgetic properties. The aim of this study was to find out if lypressin, a vasopressin analogue, produces analgesia in man. The effect of i.n. lypressin (5 and 10 I.U.) on experimental pain was tested in healthy humans. The lower dose proved high enough to produce a significant antidiuretic effect. Lypressin did not have any marked analgetic effect at these doses either on ischaemic, cutaneous thermal, or dental pain. The results indicate that lypressin cannot be used for pain relief in man at doses low enough not to produce a hazardous water retention. [ABSTRACT FROM AUTHOR]

The knowledge of patients with systemic lupus erythematosus about their disease before and after reading a patient guide was tested. The scores for incorrect answers decreased from 28 to 24% after reading the guide, showing that it increased the patients' knowledge of the disease. The patients with an academic background had the best scores before reading the guide, but they did not improve their scores as much as patients with lower educational qualifications. The differences between the groups studied were not significant in a one way analysis of variance. Forty seven questions about the psychology and coping mechanisms of the patients were factorized. These factors, together with data on the duration and severity of SLE and the age of the patient, were used in multiple linear regression analysis, but had no significant predictive value for an improvement in knowledge. The scores in psychological tests were the same before and after reading the guide. It is concluded that the patient guide for SLE increases knowledge of the disease, but does not affect the psychological response of the patient. The improvement in knowledge cannot be predicted on the basis of various psychological and clinical factors or the social background of the patient. [ABSTRACT FROM PUBLISHER]

In patients with sports-related soft-tissue injury, is cold gel more effective than placebo in reducing pain and disability? Randomized (allocation concealed), blinded (clinicians and patients), controlled trial with 28-day follow-up. A university hospital in Kuopio, Finland. 74 patients (mean age, 32 yr; 64% men) who had sustained a sports-related soft-tissue injury of the ankle, leg, knee, or hand within the previous 48 hours. Exclusion criteria were a pain score of <30 mm on the visual analog scale (VAS); pregnancy; the presence of cutaneous lesions or injuries at the site of application, thus precluding the use of gel therapy; or an injury in need of surgery or physiotherapy. Complete follow-up was achieved for 73 patients (99%). Patients were allocated to receive the active cold gel (Ice Power; Fysioline, Tampere, Finland) 4 times per day for 14 days (n = 37) or a placebo gel (n = 37). The gel was applied with the fingers by way of a slight massage. The active cold gel consisted of 3.5% menthol and 8% ethanol and adjuvants. The placebo gel contained no menthol or ethanol. Pain at rest, pain on movement during normal function, and functional disability. Secondary outcome measures were the patients' and investigators' global assessment and satisfaction with the treatment. All outcomes were measured with the 100-mm VAS (0 = no pain or disability and 100 = extreme pain or disability). Analysis was by intention to treat. Pain at rest and pain on movement decreased more in the cold-gel group than in the placebo group (Table). The difference favored the cold-gel group at each week of follow-up. The change in score in terms of functional disability also favored the cold-gel group more than the placebo group (the change in score from the baseline to 7 days was 63 to 31 for the cold-gel group compared with 62 to 48 for the placebo group; p < 0.001). Patients in the cold-gel group expressed more satisfaction with the results of treatment than did patients in the placebo group (VAS score, 71 for the cold-gel group compared with 44 for the placebo group; p < 0.001). The global assessment scores of the patients and the investigators also favored the cold-gel treatment. For patients with sports-related soft-tissue injury, cold gel was more effective than placebo gel in reducing pain and disability. [ABSTRACT FROM AUTHOR]