The effect of waiting time on health and quality of life outcomes and costs of medication in hip replacement patients: a randomized clinical trial.

OBJECTIVE: To evaluate the effect of waiting time on health and quality of life outcomes and costs of medication in total hip replacement (THR) patients in a randomized clinical trial. METHODS: 395 THR patients were recruited into the study. When placed on the waiting list, patients were randomized into a short (< or =3 months) or a non-fixed waiting time (NFWT) (>3 months) group. In the final analyses 309 patients (179 women) with a mean age of 65 years were included. Health-related quality of life (HRQoL) (generic 15D), and pain and function (modified Harris Hip Score (HHS)) were calculated when placed on the waiting list, at hospital admission, and at 3 and 12 months postoperatively. The costs of disease-specific medication were calculated at the same measurement points. All analyses were performed using the intention-to-treat (ITT) principal. RESULTS: Of the recruited patients, 309 (78%) completed the follow-up (short group 140 and non-fixed group 169 patients). The mean waiting time was 74 days in the short and 194 days in the NFWT groups. In the ITT analyses there were no statistically significant differences between the groups in the weekly use and costs of medication, HRQoL or HHS at baseline, at admission, or 3 or 12 months after surgery. The only difference was in total medication costs during the waiting time period, at EUR 83 and 171, respectively. CONCLUSIONS: The length of the waiting time did not generate different effects on the studied health and quality of life outcomes of the randomized groups. However, those in short waiting time group reached earlier better HRQoL.

Patient outcomes after simultaneous bilateral total hip and knee joint replacements.

Simultaneous arthroplasties are increasingly being performed during one single anaesthetic event. No national nosocomial surveillance systems have yet reported data on this issue. We compared patient populations undergoing bi- and unilateral total hip (THA) and total knee (TKA) arthroplasties in terms of two outcome variables, deep surgical site infections (SSI) and mortality, by analysing surveillance data from the Finnish Hospital Infection Programme (SIRO). A total of 8201 patients underwent 9831 total arthroplasties during 2001-2004. Of the prosthetic joints, 7.2% were inserted in a bilateral operation (range by hospital, 0.6-19.2%; range by procedure type, 5.2-9.9%). Patients who underwent bilateral operations were younger; more often males, and their ASA score was lower than those who underwent unilateral procedures. The rate of deep SSI in bi- and unilateral THAs and in bi- and unilateral TKAs was 0, 0.5, 1.0 and 0.9%, respectively. Following bilateral operations, four deep SSIs were detected, all from bilateral TKAs, three of which were on the second operative side. In these three cases, single doses of antimicrobial prophylaxis were administered 115, 155 and 218 min before incision (median time in unilateral operations: 47 min). According to multi-variate analysis, bilateral operations were not an independent risk factor for deep SSIs. Mortality did not differ between bi- and unilateral THAs or TKAs. Our surveillance data indicate that simultaneous bilateral surgery did not increase the risk of deep SSIs or death after THA and TKA. Bilateral operations may, however, require specific guidelines regarding antimicrobial prophylaxis.

Surgical versus conservative interventions for anterior cruciate ligament ruptures in adults.

BACKGROUND: Anterior cruciate ligament rupture is a common knee injury. Surgical treatment, usually involving reconstruction of the ligament, is widely used especially in active individuals. OBJECTIVES: Evaluation of the effect of surgical treatment compared with conservative treatment of anterior cruciate ligament (ACL) rupture. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to January Week 3 2005), EMBASE (1988 to 2005 Week 05), MEDIC (1978 to January 1999), Current Contents (9.2.1998 to 1.2.1999), BIOSIS (1970 to December 1998), reference lists of articles and consulted trialists and experts. SELECTION CRITERIA: All randomised and quasi-randomised trials that compared surgical with conservative treatment of ACL rupture in adults. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, data extraction and quality assessment. MAIN RESULTS: Two poor quality randomised trials conducted in the early 1980s were included in the review. The two trials differed considerably and no data pooling was done for the few shared outcome measures. One quasi-randomised trial of 167 people with a complete ACL rupture treated with repair or augmented repair versus conservative treatment found no difference in the return to sports activities between people treated surgically and those treated conservatively. Measures of knee stability and functional (Lysholm) knee scores were higher in surgically-treated participants. By the end of the follow-up period (average 55 months), three people treated with repair only and 16 treated conservatively had had ACL reconstruction. The other trial included 157 people with ACL injury. This found that conservatively-treated participants recovered from their injury more rapidly but, at the last follow up (minimum 13 months), the functional outcome was similar in both treatment groups. A large proportion of participants experienced some temporary discomfort after surgery and there were some more serious postoperative complications. There was less knee instability in surgically-treated participants and a tendency to fewer subsequent operations in the longer term. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to determine whether surgery or conservative management was best for ACL injury in the 1980s, and no evidence to inform current practice. Good quality randomised trials are required to remedy this situation.

Radiofrequency denervation for neck and back pain. A systematic review of randomized controlled trials.

BACKGROUND: The diagnosis of cervical or lumbar zygapophyseal joint pain can only be made by using local anesthesia to block the nerves supplying the painful joint. There is a lack of effective treatment for chronic zygapophyseal joint pain or discogenic pain. Radiofrequency denervation appears to be an emerging technology, with substantial variation in its use between countries. OBJECTIVES: To assess the effectiveness of radiofrequency denervation for the treatment of musculoskeletal pain disorders. SEARCH STRATEGY: We searched MEDLINE, PsycLIT, and EMBASE from start to February 2002, plus the Cochrane Library 2002, Issue 2. The references of identified articles were checked and three experts in the field of radiofrequency treatment were consulted to identify studies we might have missed. SELECTION CRITERIA: Randomized controlled trials (RCTs) of radiofrequency denervation for musculoskeletal pain disorders, with no language or date restrictions. DATA COLLECTION AND ANALYSIS: Two reviewers selected RCTs that met predefined inclusion criteria, extracted the data, and assessed the main results and methodological quality of the selected trials, using standardized forms. Qualitative analysis was conducted to evaluate the level of scientific evidence. MAIN RESULTS: We found only nine articles, reporting on seven relevant RCTs. Six of the seven were considered to be high-quality. The selected trials included 275 randomized patients, 141 of whom received active treatment. One study examined cervical zygapophyseal joint pain, two cervicobrachial pain, three lumbar zygapophyseal joint pain, and one discogenic low-back pain. The study sample sizes were small, follow-up times short, and there were some deficiencies in patient selection, outcome assessments, and statistical analyses. The level of scientific evidence for the short-term effectiveness of radiofrequency denervation was limited for cervical zygapophyseal joint and cervicobrachial pain, and conflicting for lumbar zygapophyseal joint pain. There was limited evidence suggesting that intradiscal radiofrequency thermocoagulation was not effective for discogenic low-back pain. REVIEWER'S CONCLUSIONS: The selected trials provide limited evidence that radiofrequency denervation offers short-term relief for chronic neck pain of zygapophyseal joint origin and for chronic cervicobrachial pain; conflicting evidence on the short-term effect of radiofrequency lesioning on pain and disability in chronic low-back pain of zygapophyseal joint origin; and limited evidence that intradiscal radiofrequency thermocoagulation is not effective for chronic discogenic low-back pain. There is a need for further high-quality RCTs with larger patient samples and data on long-term effects, for which current evidence is inconclusive. Furthermore, RCTs are needed in non-spinal indications where radiofrequency denervation is currently used without any scientific evidence.

Scoliosis associated with lumbar spondylolisthesis. A clinical survey of 190 young patients.

A series of 190 patients with lumbar spondylolisthesis treated operatively during the years 1948-80 at the mean age of 15.2 years (8-19 years) and reexamined 4-36 years (mean 11.2 years) later are presented. In 92 of them (48%) scoliosis (more than 5 degrees) in association with olisthesis was seen. The slipping affected the fifth segment in 90 and fourth segment in two patients. The female predominance was characteristic in the scoliotic group. Dysplastic changes of the posterior arc were more often seen in the group of patients with scoliosis than in the nonscoliotic group, and they also presented a more severe grade of slipping and lumbosacral kyphosis. The curve was usually mild and was situated in the lumbar area. Patients with a higher degree of lumbosacral kyphosis and more severe slipping also had a statistically higher degree of lumbar scoliosis. Operative treatment of spondylolisthesis consisted of posterior or posterolateral fusion in situ, but two patients were treated using ventral fusion and three severe cases with removal of loose posterior element. Lumbar scoliosis classified as sciatic type disappeared in 25 out of 39 patients after lumbosacral fusion, suggesting the "sciatic muscle spasm" as an etiologic factor. The torsional type of curve resulting from asymmetrical slipping of the vertebra was also corrected in 19 out of 28 cases after fusion. At follow-up patients with remaining lumbar scoliosis represented more low-back pain than those without any curve. In our opinion lumbosacral fusion is indicated before lumbar curve changes to structural scoliosis in symptomatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Reoperations after lumbar disc surgery: a population-based study of regional and interspecialty variations.

STUDY DESIGN: A follow-up study using nationwide administrative databases. OBJECTIVES: To explore rates of reoperation after lumbar disc surgery and their regional and interspecialty variations. SUMMARY OF BACKGROUND DATA: In many Western countries, rates of lumbar disc surgery display significant geographic variations suggesting varying treatment criteria among operating surgeons. Few population-based studies have explored the risk of reoperation after disc surgery, and regional or interspecialty variations in the reoperations are unknown. METHODS: Patients who underwent lumbar spine surgery from January 1, 1987 through December 31, 1995, were identified in the Finnish Hospital Discharge Register. Data on the patients' initial disc operations, subsequent operations, and cause-of-death records were linked using personal identification codes. The Kaplan-Meier method and proportional hazard model were used to analyze risks of reoperation after initial surgery, according to hospital catchment area rates of disc surgery and for neurosurgical and orthopedic patients of university hospitals. RESULTS: 12.3% of 25,359 surgical patients with herniated lumbar discs underwent subsequent lumbar operations corresponding to the cumulative risk of 18.9% in the 9-year follow-up. Reoperation rates increased during the study period with the recent patient cohorts exhibiting risks. The reoperation risk showed a systematic geographic variation: the higher the regional disc surgery rate, the higher the reoperation risk. Overall, neurosurgical patients had a higher reoperation risk than orthopedic patients (relative risk [RR]: 1.57, 95% confidence interval [CI]: 1.17-2.10), but this was not a uniform finding. CONCLUSIONS: The reoperation risk after disc surgery increased during the study period and was higher in hospital catchment areas with higher overall discectomy rates. The reoperation risks varied among the university hospitals but tended to be higher for neurosurgical rather than for orthopedic patients.

The role of mast cells in disc herniation inflammation.

STUDY DESIGN: A study of herniated lumbar disc tissue samples and control disc material to determine the presence of mast cells in disc herniations. OBJECTIVES: To analyze whether mast cells have any involvement in disc herniation pathophysiology and lumbar pain, because mast cells may have an important role in acute and chronic inflammatory responses. SUMMARY OF BACKGROUND DATA: Studies of inflammatory cells, biochemical mediators of inflammation, and tissue degrading enzymes have suggested that these factors may be involved--and perhaps play an important role--in the pathophysiology of lumbar pain and radiculopathy. Mast cells are known to play an important role in acute and chronic inflammatory responses. It was therefore of interest to clarify their possible role in intervertebral disc herniation inflammation. METHODS: Fifty herniated lumbar discs from 50 patients who had undergone disc surgery and three normal control discs were obtained. Sections from every disc then were examined histologically and immunocytochemically for mast cells by using monoclonal antibodies to either of two types of specific proteases of mast cells, tryptase and chymase. RESULTS: By none of the methods could any mast cells be observed in any of the control disc samples. With toluidine blue staining, mast cells were observed in 9 of 50 (18%) of discs. Mast cells immunoreactive to either tryptase or chymase were observed in 10 of 50 disc samples (20%) and immunoreactive for tryptase and chymase simultaneously in 4 of 50 disc samples (8%). However, the majority of the samples studied (80%) demonstrated immunoreactivity to neither tryptase nor chymase. Among the samples studied were five disc protrusions that totally lacked mast cells. CONCLUSIONS: A minority of disc herniations exhibited mast cells, as verified by toluidine blue staining and immunocytochemistry. The results may suggest a role of mast cells in intervertebral disc herniation inflammation, but only in a subset of these cases. Massive infiltration by mast cells never was observed.

Inflammatory cells, motor weakness, and straight leg raising in transligamentous disc herniations.

STUDY DESIGN: Possible statistically significant relationships between inflammatory cells and either motor weakness or straight leg raising were determined. OBJECTIVES: To look for any clinically relevant links between inflammatory cells in disc herniations and signs of radiculopathy. SUMMARY OF BACKGROUND DATA: Many studies have during recent years shown a presence of various types of inflammatory cells in disc herniations, but their clinical relevance has been questioned. To be clinically relevant, a presence of inflammatory cells should show a clear relationship to clinical evidence of nerve root involvement. Macrophages repeatedly demonstrated in a high proportion of disc herniations studied are of particular interest. Their major role may be in disc herniations tissue resorption and not in sciatica. METHODS: A total of 96 disc herniations, all transligamentous, were analyzed by immunohistochemistry for presence of macrophages, T or B lymphocytes, and activated T lymphocytes separately. From recorded patient data, motor weakness and straight leg raising data were compared with a presence or absence of abundant (+ = at least 20 cells in a group) inflammatory cells. When not abundant, inflammatory cells were classified as "only few cells" (+) and grouped together with "no cells" (-). Patients with or without motor weakness were compared. Straight leg raising was compared for a positive (at <70 degrees ) or a negative test, and separately using the median as cut-off value. Groups were compared by chi-square analysis with the level of statistical significance set at P<0.05. RESULTS: None of the four inflammatory cell types showed any significant association with motor weakness. Nor was any association observed when comparing positive and negative straight leg raising. With the median (straight leg raising = 47.5 degrees ) as cut-off, only activated T cells showed a weak (chi2 = 4.40, P<0.05) relationship with tighter straight leg raising, but none of the other cell types did. Even when straight leg raising was < 47.5 degrees, three times more disc herniations lacked (n = 34) inflammatory cells than showed (n = 13) inflammation. In a subgroup of only sequestrated discs, the findings were similar. However, in the patients with a bilaterally positive straight leg raising (n = 25), the prevalence of at least one inflammatory cell type was much higher in sequestrated discs (80%) than in extrusions (33%). This may suggest more subtle interrelationships between type of disc herniation, straight leg raising, and inflammatory cells. CONCLUSIONS: The results of this study do not support a clinically relevant role for disc herniation inflammatory cells in sciatica. For the cells to be clinically relevant, a strong relationship between a presence of inflammatory cells and either or both of motor weakness and a tight straight leg raising should have been observed. The authors conclude that macrophages, which have been demonstrated in a high proportion of disc herniations in previous studies, are probably more important for disc tissue resorption processes than for producing sciatica. Other types of inflammatory cells are more rarely observed and may have no clinical meaning at all. However, more subtle interrelationships, considering the various types of disc herniations, should be further explored.

A comparative immunohistochemical study of inflammatory cells in acute-stage and chronic-stage disc herniations.

STUDY DESIGN: Herniated lumbar disc specimens were obtained from patients undergoing surgical discectomy for persistent radicular pain (radiculopathy) and stained for inflammatory cells to determine their occurrence in relation to the duration of radicular pain and to analyze the role of the time factor in the inflammatory response. OBJECTIVES: To analyze the presence of inflammatory cells and their involvement in the pathophysiology of radicular pain and to determine whether there is a clear difference in the occurrence of inflammatory cells between the earlier phase of radicular pain (after herniation) and the later chronic stage. SUMMARY OF BACKGROUND DATA: Previously, inflammatory cells were reported in herniated disc tissues, and macrophages were most prevalent. Biologically active inflammatory mediators have also been repeatedly observed. However, there have been no observations regarding possible differences in the occurrence of inflammatory cells in radicular pain of different durations. METHODS: Forty-four herniated lumbar discs were obtained from 44 patients undergoing disc surgery. Two groups of 22 age- and gender-matched patients with comparable affected disc levels were studied. In the first group (acute group) pain duration ranged from 3 days to 21 days. In the second group (chronic group) pain duration was 6 months or longer. All disc herniation specimens were subjected to indirect immunocytochemistry to study and compare the presence of inflammatory cells. RESULTS: Inflammatory cells, predominantly macrophages, were observed in both groups. Macrophages were abundantly present in eight (36%) disc samples in the acute group; in three (14%) samples only few scattered macrophages were observed. In the chronic group, in nine (41%) disc samples, abundant macrophages were observed; in six (27%) there were a few scattered macrophages. In the acute group, in three (14%) disc samples abundant activated T lymphocytes were observed; in two (9%) there were only a few activated T lymphocytes, whereas in the chronic group abundant activated T lymphocytes were not seen; only a few scattered activated T lymphocytes were observed in five (23%) disc tissue samples. In two (9%) samples in the acute group, B cells were abundantly present, and in two (9%) only a few B cells were observed. In the chronic group, abundant B cells were seen in no samples, and only a few B cells were noted in one (5%) sample. Only in the acute group and only in lateral disc herniations were abundant lymphocytes observed. In disc samples from intraspinal herniations, acute and chronic, there were only abundant macrophages, not lymphocytes. CONCLUSIONS: Because of the small size of the study groups and the low prevalence particularly of lymphocytes in both groups, no major group differences were noted. The prevalence of macrophages was highest, similar in both groups, and was similar to the results in prior studies. The results indicate no major differences in the occurrence of inflammatory cells in acute and chronic disc herniations. They also indicate that only macrophages may have a clinical relevance in disc tissue inflammation.

Progression of spondylolisthesis in children and adolescents. A long-term follow-up of 272 patients.

The radiologic progression of spondylolisthesis during a long-term follow-up was studied in 272 children and adolescents. There were 134 girls and 138 boys. The mean age at the first visit was 14.3 years (girls, 13.8 years; boys, 14.9 years). The radiologic follow-up time was 14.8 years on average (range, 5-32). The operation was done in 190 patients younger than 20 years of age. Fusion in situ, using a posterior or posterolateral technique, had no statistically significant effect on progression. Surgically treated patients did not differ from conservatively treated patients. Ninety percent of the slip, on average, had already occurred at the first radiologic examination compared with the final amount of slip. More than 10% progression occurred in 62 patients, mainly within the first year postoperatively or after the first examination. Progression of the lumbosacral kyphosis and sinking of the vertebral body was noted in severe slips. Although female gender and dysplasia (spina bifida) at the lumbosacral junction were more frequent in severe slips, they statistically had no value in predicting progression. A wedge form of L5 or sacral rounding also had no prognostic value. These were secondary to the slip and expressed it but did not predict it. The only radiologic variable with predictive value of progression was the percentage amount of the primary slip. In age groups corresponding to the growth spurt in early puberty (girls, 9-12 years; boys, 11-14 years), there was a tendency to progress.

Prevalence, morphology, and topography of blood vessels in herniated disc tissue. A comparative immunocytochemical study.

STUDY DESIGN: Ninety disc herniations removed during surgery were studied by immunocytochemistry, using two different endothelial cell markers, to study the prevalence, morphology, and topography of blood vessels in disc herniations. OBJECTIVES: To increase the specific localization of even very small blood vessels present in disc herniations by using specific antibodies to endothelial cells; to study blood vessels comparatively with two different endothelial cell antibodies, comparing their prevalence; and to study blood vessel morphology and topographic relationships of blood vessels to other tissue elements, particularly disc cells. SUMMARY OF BACKGROUND DATA: In many previous macroscopic studies and in studies using conventional histologic methodology, blood vessels have been observed in degenerated and injured intervertebral discs. In a smaller patient sample, the authors previously observed blood vessels in approximately 80% of disc herniations by immunocytochemistry, the blood vessels co-localizing with macrophage cells. Many of these blood vessels are the product of very active neovascularization after disc tissue injury. The presence of such blood vessels has not, however, been studied in greater detail or in larger patient samples. Immunocytochemistry offers superior visualization and more specific localization and was thus used in the present study. METHODS: Thin frozen sections from 90 disc herniations were immunostained in parallel with von Willebrand factor and Ulex europaeus antibodies, both of which localize endothelial cells specifically. Indirect immunocytochemistry by avidin-biotin-peroxidase complex or alkaline phosphatase-antialkaline phosphatase were used for immunolocalization. Blood vessels were classified as being: +, abundant: (+), very few; or +, totally absent. RESULTS: The prevalence of blood vessels in disc herniations was found in 82 of 90 (91%) disc herniations with von Willebrand factor antibody and in 75 of 90 (83%) disc herniations with Ulex europaeus antibody. In 59 disc herniations (66%), blood vessels were observed with both antibodies in parallel, whereas they were observed with neither antibody in only six of 90 disc herniations. Furthermore, the ratio of abundant to very few blood vessels was 73:9 with von Willebrand factor antibody and 63:12 with Ulex europaeus antibody, further supporting the abundance of blood vessels in disc herniations. Blood vessels were most prevalent in sequestrated discs, but they were also observed in six of eight protrusions. Dense blood vessel networks were observed to penetrate the disc tissue, and blood vessels were also present in areas of inflammatory cell infiltration. Topographically, blood vessels were, on several occasions and with both antibodies, seen to pass close by or to surround disc cells. CONCLUSIONS: By immunocytochemistry with endothelial cell markers, blood vessels can be observed to be numerous, and their prevalence in herniated discs is very high, presumably as a result of a very intense neovascularization process after the disc injury. A close apposition to disc cells may suggest attempts to increase the nutrition of these cells and will influence the metabolism of the cells.

Immunocytochemical localization of immunoglobulins in disc herniations.

STUDY DESIGN: Disc herniation and control discs were studied for the presence of immunoglobulins immunocytochemically. OBJECTIVES: To study a possible presence of immunoglobulin complexes in herniated disc tissue and to locate them at the tissue level by immunocytochemistry; to compare immunohistologic findings with those obtained in control disc tissue; and to compare the prevalences of immunoglobulin M and immunoglobulin G. SUMMARY OF BACKGROUND DATA: In herniated disc tissue, high activity of inflammatory phospholipase A2 was previously demonstrated, and inflammatory cells were noted immunohistochemically. Immunoglobulins G and M were observed biochemically but have not been located at the tissue level. METHODS: Fifty-two disc herniations and three macroscopically normal fresh cadaver discs were managed by an identical immunocytochemical protocol, using monoclonal antihuman antibodies to immunoglobulins M and G. RESULTS: In 29 of 52 disc herniations (56%), immunoglobulin M deposits were observed, and in 18 of 52 disc herniations (35%) immunoglobulin G could be demonstrated. Almost all the disc herniations where immunoglobulin G was present also contained immunoglobulin M deposits (except for two). In the control discs studied, neither immunoglobulin could be observed immunohistochemically. The immunoglobulin deposits were noted in areas where blood vessels were also present. Morphologically, immunoglobulin immunoreactivity resembling immune complexes was observed. CONCLUSIONS: The results lend support to previous suggestions of inflammation and immune reaction in disc herniations, including previous biochemical studies suggesting immunoglobulin deposition. The exact role of the demonstrated immunoglobulins in disc tissue pathophysiology will have to be clarified further.

Basic fibroblast growth factor immunoreactivity in blood vessels and cells of disc herniations.

STUDY DESIGN: Basic fibroblast growth factor immunoreactivity was studied in disc herniation tissue. OBJECTIVES: The first objective was to analyze in which tissue components, if any, fibroblast growth factor is expressed in the disc herniation. The second objective was to compare such expression with that in fresh cadaver disc tissue. SUMMARY OF BACKGROUND DATA: Disc herniation tissue contains vascular ingrowth, which promotes the formation of granulation tissue. Fibroblast growth factor is a potent inducer of angiogenesis and also regulates extracellular proteolysis. METHODS: Twenty-seven disc herniation tissue and five macroscopically normal fresh cadaver discs were treated with an identical immunohistochemical protocol. Serial frozen sections were stained with a polyclonal basic fibroblast growth factor antibody and a polyclonal antibody to von Willebrand factor, which localizes endothelial cells. The immunostaining data were compared with relevant clinical data. RESULTS: Histologically, 74% of the samples contained anulus fibrosus and 59% nucleus pulposus. Basic fibroblast growth factor immunoreactivity was detected in 81% of the samples. There were immunopositive small blood vessels and scattered immunopositive disc cells (67%). Not all observed blood vessels were basic fibroblast growth factor immunopositive. In control discs, no immunoreactivity was observed. CONCLUSIONS: The observed presence of fibroblast growth factor in small blood vessels suggests an active angiogenesis as a result of disc injury. Cellular expression of fibroblast growth factor may be linked to proteolytic activity in disc extracellular matrix.

Comparison of the prevalence of inflammatory cells in subtypes of disc herniations and associations with straight leg raising.

STUDY DESIGN: The prevalence of inflammatory cells in 205 disc herniations (DHs) and nine macroscopically normal discs for comparison was studied immunohistochemically. Inflammatory cells were separately analyzed in subtypes of DH. Immunohistochemical data were related to clinical parameters, the straight leg raising test (SLR) in particular. OBJECTIVES: The objectives of the study were to compare the occurrence of inflammatory cells in various subtypes of DH and to determine the association between clinical data and inflammatory cell occurrence in a more extensive sample of DH, with separate analysis of DH subtypes. SUMMARY OF BACKGROUND DATA: Previous studies have suggested a common occurrence of inflammation and inflammatory cells, particularly macrophages, in DHs. No studies on any larger material comprising different subtypes of DH have been done. METHODS: For immunohistochemistry the alkaline phosphatase antialkaline phosphatase method was used. Monoclonal antibodies to T cells in general (CD2), activated T cells (CD25), B cells (CD22), and macrophages (CD68) were used. Obtained immunostaining results were then compared with clinical data, e.g., duration of pain, SLR, and type of DH (sequesters 86, extrusions 103, protrusions 16). Associations were studied by the chi2 test or Fisher's exact test, as applicable (level of significance P < 0.05). RESULTS: Abundant T cells were seen in 17% of the 205 DHs, activated T cells in 17%, B cells in 16%, and macrophages in 37%. All cell types were 2-3 times more prevalent in sequestrated discs than in extrusions. In protrusions macrophages were abundantly seen in 25% (4 of 16) and no other inflammatory cells. In patients with positive SLR and a sequestrated disc abundant lymphocytes were seen three times more often than in extrusions. When patients with bilaterally negative SLR were compared with those with tight SLR (< or =30 degrees ) with respect to inflammatory cell occurrence, some significant differences were noted (CD68, P < 0.025; CD25, P = 0.04). A comparison between SLR bilaterally positive and bilaterally negative also showed associations for all four inflammatory cell types (P = 0.016 to P = 0.029). There was no correlation between inflammatory cells and duration of pain. Abundant inflammatory cells were never seen in control discs. CONCLUSIONS: When SLR was positive and the DH type was sequestered, inflammatory cells were most commonly seen. Our results showed some statistically significant associations between inflammatory cells and SLR, most clearly when comparing bilaterally positive and negative SLR. Interestingly, a bilaterally positive SLR showed an association with all four inflammatory cell types analyzed. Tight SLR also showed an association, particularly with macrophages. In addition to tissue resorption, they may participate in sciatic pain. Even though lymphocytes were less prevalent, they may have some role in sequestered discs and bilaterally positive SLR.

Straight leg raising test and lumbar cerebrospinal fluid levels of vasoactive intestinal polypeptide and somatostatin in patients with low back pain.

STUDY DESIGN: Straight leg raising was recorded before myelography in 77 patients. At myelography, samples of cerebrospinal fluid were drawn and later analyzed for neuropeptides vasoactive intestinal polypeptide and somatostatin. OBJECTIVES: The study sought to examine correlations, if any, between a positive straight leg raising test and cerebrospinal fluid neuropeptide levels. METHODS: The straight leg raising test was recorded for all patients before a myelography examination was performed because of intractable leg pain symptoms. Forty-seven of the patients were men and 30 were women. Cerebrospinal fluid samples were obtained from all patients upon myelography. Levels of the neuropeptides vasoactive intestinal polypeptide and somatostatin were analyzed in a blind manner by radioimmunoassay, using commercially available radioimmunoassay kits. RESULTS: The results are compatible with previous observations that suggest cerebrospinal neuropeptide levels are altered in conjunction with neural injury or pain syndromes. In the present mixed back pain patient population, which included radicular pain symptoms due to disc herniation and lumbar stenosis, alterations in vasoactive intestinal peptide levels in particular were observed with a positive straight leg raising test. CONCLUSIONS: Nerve root injury, as suggested by a positive straight leg raising test, appears to be neurochemically linked to altered cerebrospinal fluid vasoactive intestinal peptide levels.

Symptomatic lumbar spondylolysis. Neuroimmunologic studies.

OBJECTIVES: This study characterized the defect using neuroimmunologic and inflammatory cell analysis. SUMMARY OF BACKGROUND DATA: Spondylolysis/spondylolisthesis is thought to be caused by a congenital weakness and mechanical stress causing a fracture associated with defective healing. Most of the spondylolysis patients are asymptomatic and the mechanisms of pain in symptomatic patients are unknown. METHODS: Tissue from the spondylolysis defect was collected from seven patients undergoing posterolateral fusion operations. RESULTS: Histologic examination disclosed delayed union/pseudoarthrosis with fibroblasts and macrophages in a pseudosynovial lining membrane and occasional perivascular infiltrates containing mainly CD2 lymphocytes and CD11b monocytes/macrophages. In a vascularized connective tissue stroma PGP 9.5, synaptophysin and neurofilament staining disclosed perivascular nerves, which did not extend to the synovial lining layer and which mainly represented postganglionic sympathetic nerve fibers but also calcitonin gene-related peptide and substance P containing sensory fibers. CONCLUSIONS: Pain in spondylolysis/spondylolisthesis might derive from the spondylolytic defect itself, probably from stretching of the local neural elements rather than from their sensitization/stimulation by local inflammatory mediators. The resemblance of neuroimmunohistochemical changes compared with those reported in the nonunion of long bones and the sparsity of stromal innervation, indicate that the characteristic defective healing is in part due to lack of neurogenic influences.

Immunohistochemical demonstration of sensory and autonomic nerve terminals in herniated lumbar disc tissue.

STUDY DESIGN: Thirty-five lumbar disc herniations removed at surgery were studied by indirect immunocytochemistry. OBJECTIVES: To localize immunohistochemically both sensory and autonomic nerve terminals in disc herniations. SUMMARY OF BACKGROUND DATA: Using various more or less specific histologic and histochemical methods, investigators have reported the presence of free nerve terminals in disc tissue. However, very few studies have, to date, convincingly demonstrated nerve terminals in disc tissue that morphologically resemble the tiny nerve terminals of sensory and autonomic nerve fibers. METHODS: Amplification of the peroxidase reaction product in avidin-biotin-peroxidase complex immunostaining by the glucose oxidase-diaminobenzidine-nickel sulfate method was used to visualize small punctate nerve terminals at high magnification. Thin frozen sections from disc herniation tissue prefixed in Zamboni fixative were incubated with antibodies to synaptophysin to visualize nerve terminals in general, and with antibodies to substance P and C-flanking peptide of neuropeptide Y to further characterize nerve terminals as either sensory or sympathetic. RESULTS: Nerve terminals could be demonstrated in 29 (83%) of the 35 disc herniations. They were observed with the synaptophysin antibody in 17 of 35 (49%) disc herniations, with substance P in 16 of 35 (46%) disc herniations, and with C-flanking peptide of neuropeptide Y in 13 of 35 (37%) disc herniations. Morphologically, the nerve terminals were seen as tiny immunoreactive dots. Some of the nerve terminals were observed close to disc cells, possibly suggesting direct interaction. CONCLUSIONS: Small nerve terminals in disc herniations, both sensory substance P endings and sympathetic C-flanking peptide of neuropeptide Y endings, could be involved in mechanisms of discogenic pain, disc tissue neurogenic inflammation, tissue repair processes after injury, and control of local blood circulation in the newly formed blood vessels. Disc cells may be directly affected by the neuropeptides released from nearby nerve terminals.

Surgical treatment of severe isthmic spondylolisthesis in adolescents. Reduction or fusion in situ.

Twenty-two adolescent patients with severe (more than 50%) slip were surgically treated. Eleven were reduced with Magerl/Dick transpedicular screw devices and fused posteriorly from L4 to S1, and 2 weeks later anteriorly L5-S1; the other 11 were fused in situ L4-S1 (6 patients) or L5-S1 (5 patients) using a circumferential (6 patients), anterior (4 patients) or posterolateral (1 patient) technique without instrumentation. The two groups were comparable as to age at operation, age at follow-up, follow-up time, and preoperative radiologic measurement of the slip, lumbosacral kyphosis, and clinical findings. The mean follow-up times were 56.5 and 59.8 months, respectively. In the reduction group an improvement in the slip of 36.1 percentage points was achieved as compared with 7.7 percentage points in the in situ-fusion group. The sagittal rotation angle improved by 11 in the reduction group and worsened by 2.8 in the in situ-fusion group. There were no differences between the groups in the functional tests or clinical findings concerning pain. Subjective assessment was good in both groups at follow-up; that is, the pain had disappeared. Mean operation time and intraoperative blood loss were significantly higher in the reduction group. Reduction procedures were also associated with a higher number of complications and reoperations. No neurologic complications, however, occurred in the reduction group. Based on this study, in situ fusions are to be preferred in adolescents with severe spondylolisthesis.

Neuroimmunohistochemical analysis of peridiscal nociceptive neural elements.

Twenty-three perioperative tissue samples from lumbar disc operations on 11 patients were studied immunohistochemically using the sensitive avidin-biotin-peroxidase complex (ABC) method and specific heterologous antisera for the presence of neurofilament-positive neural elements containing nociceptive neuropeptides substance P (SP) and/or calcitonin gene-related peptide (CGRP). Histologically, neural elements were especially abundant in the posterior longitudinal ligament, there being also a few demonstrable nerves in the peripheral anulus fibrosus. These nerves often showed a co-localization of cytoskeletal neurofilaments together with SP and/or CGRP immunoreactivity. It is suggested that pressure and chemical irritation of nociceptive nerves dependent on degenerated discs excite sensory neural elements, especially in the posterior longitudinal ligament and possibly also in the peripheral parts of the anulus fibrosus, while the disc itself, at least if not penetrated by vascular granular tissue, is painless and neuroanatomically lacks a structural basis for pain perception.

A controlled immunohistochemical study of inflammatory cells in disc herniation tissue.

STUDY DESIGN: The presence and abundance of inflammatory cells was studied immunocytochemically in lumbar disc herniations (DH) and macroscopically normal discs for comparison. OBJECTIVES: The objective of the study was to characterize inflammatory cells that appear in herniated disc tissue and to study the relative abundance of various types of inflammatory cells. SUMMARY OF BACKGROUND DATA: Only few macrophages were observed in control discs, whereas abundant macrophages were present in half of the DH. Other types of inflammatory cells were less often abundant in the present material. In about a third of the DH interleukin-1 beta-expressing cells were also observed. METHODS: Twenty-four DH and control tissue from five discs were studied immunocytochemically, using specific monoclonal antibodies to various types of inflammatory cells and interleukin-1 beta. The results were compared with corresponding clinical data. Macrophages were studied with an antibody to CD68 antigen and Ber-MAC3 antibody separately. RESULTS: The obtained results suggest a variable inflammatory cell response in DH, which seems to be often dominated by macrophages at the time of operation. Thus previous suggestions of sometimes very active inflammation in DH tissue are supported. CONCLUSIONS: Inflammation may be important in disc tissue pathophysiology, possibly also in discogenic pain mechanisms.