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Background: Previous studies have shown that the long-term clinical outcome does not correlate with the radiographic outcome in patients treated with Harrington instrumentation for adolescent idiopathic scoliosis. Cotrel-Dubousset instrumentation has been reported to provide better correction radiographically, but it is unclear whether it provides better long-term clinical or functional outcomes. We are not aware of any long-term studies comparing Harrington and Cotrel-Dubousset instrumentation.Methods: Seventy-eight patients in whom adolescent idiopathic scoliosis was treated with Harrington instrumentation and fifty-seven in whom it was treated with Cotrel-Dubousset instrumentation participated in this study. The mean duration of follow-up was 20.8 years for the Harrington instrumentation group and 13.0 years for the Cotrel-Dubousset instrumentation group. The mean age at the time of follow-up was thirty-six years and twenty-eight years, respectively. Radiographs were made preoperatively and at the two-year and final follow-up examinations. The Scoliosis Research Society questionnaire was completed, a physical examination was performed, and spinal mobility and non-dynamometric trunk strength were measured at the final follow-up visit.Results: The mean preoperative Cobb angle of the thoracic curves was 53 degrees in the Harrington instrumentation group and 55 degrees in the Cotrel-Dubousset instrumentation group. The mean numbers of vertebrae included in the instrumentation were 10.7 and 9.9, respectively. At the two-year follow-up evaluation, the mean postoperative Cobb angles were 38 degrees and 25 degrees, respectively (p < 0.0001). At the final follow-up evaluation, the mean angles were 45 degrees and 32 degrees (p < 0.0001). No significant difference in thoracic kyphosis or lumbar lordosis was observed between the study groups at the final follow-up evaluation. The average score on the Scoliosis Research Society questionnaire was 97 points in both groups. Measurements of non-dynamometric trunk strength corresponded with age and sex-adjusted reference values, on the average, but patients with Cotrel-Dubousset instrumentation performed significantly better in the squatting test (p = 0.010). Abnormal lumbar extension and trunk side-bending were significantly more common in the Harrington instrumentation group (p = 0.050 and p = 0.0061, respectively). Complications were recorded for nine (12%) of the patients treated with Harrington instrumentation and fifteen (26%) of those treated with Cotrel-Dubousset instrumentation (p = 0.027).Conclusions: Cotrel-Dubousset instrumentation yielded better long-term functional and radiographic outcomes in patients with adolescent idiopathic scoliosis than did Harrington instrumentation. However, complications were more common in the Cotrel-Dubousset instrumentation group. [ABSTRACT FROM AUTHOR]

Background: Scoliosis with spondylolisthesis was described in 4.4-48%. No information on clinical impact or outcome is available., Purpose: To determine the prevalence of this pathology and to investigate its affect on the course of adolescent idiopathic scoliosis (AIS)., Methods: A retrospective comparative study using patients' records, radiographs, the national inpatient registry, and Patient-rated outcome measures (PROM): Oswestry disability index (ODI), modif.SRS-24 questionnaire, WHO-Quality of life index (WHOQoL), Numerical rating scale (NRS) for pain. Clinical follow-up time was 4.4 (4.3) years, and follow-up rate was 95%. PROM follow-up time 26.4 (2.8) years χ 2 statistics and t-tests were applied. Significance threshold was set at P < 0.05., Results: Out of 1531 consecutive Caucasian AIS patients, aged 13.9 (1.8) years, primary curve 29.2 (11.5) drs., 120 (7.8%) had low-grade isthmic L5-slip of mean 15.0 (8.3)% (Study group = S). The distribution of the curve types in the study group was comparable to the remaining 1411 patients with AIS only. In comparison with a pair-matched control group (C) at admission, back pain interfering with activities of daily living had 4.2% of the study group and 1.7% of the control group, at clinical follow-up 2.6/4.2% resp. (n.s.). Between groups S/C, there was no significant difference concerning scoliosis treatment: observation 38.3/45.8%, bracing 48.3/46.6%, surgery 10.8/10.2%. Results of treatment were equal in both groups. Long-term outcomes (ODI, SRS-24, WHOQoL, NRS-back/leg pain) were comparable., Conclusions: The prevalence of low-grade isthmic L5-spondylolisthesis in AIS patients was 7.8%. The presence of low-grade isthmic spondylolisthesis did not influence the curve type of AIS nor did it affect the course or long-term outcome. These slides can be retrieved under Electronic Supplementary Material.

Aim: To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs., Methods: We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients., Results: Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations. The overall patient outcome, including joint health and patient satisfaction, was good in 10/15, fair 4/15 and poor in 1/15. No deep infections were observed. Cost analysis was most beneficial in low responders and in two immune-tolerized, high responder patients. In all cases, factor replacement comprised the main treatment costs., Conclusion: Our experience supports the initial use of bypassing agents as well as preoperative immune-tolerance induction when possible. Despite the challenges of haemostasis and severe joint disease, total joint arthroplasty can reach a good outcome, even in inhibitor patients. The risk for deep infection might be smaller than previously reported. Individual planning, intense multidisciplinary teamwork and execution of operations should be centralised in a professional unit., Competing Interests: Conflict-of-interest statement: The authors stated that they had no competing interests, which might be perceived as posing a conflict or bias.

The coumarin composition of Peucedanum palustre (L.) Moench populations growing in Finland was investigated. A total of 132 flowering P. palustre specimens from 43 locations in southern and central Finland were collected, divided into root, stem, leaf, and umbel samples, and analyzed by HPLC. HPLC coupled to high-resolution mass spectrometry was used to aid the identification of coumarins. A total of 13 coumarin-structured compounds were quantitatively analyzed from the samples. The coumarin profile of root samples was found to differ from the aerial plant parts. The main coumarins in roots were oxypeucedanin and columbianadin. In aerial parts, peulustrin isomers were the most abundant coumarin components. Umbels and leaves also contained a considerable amount of umbelliprenin, which was only found in traces in roots. Based on hierarchical cluster analysis of the coumarin profiles, some populations shared common characteristics. The most distinct property connecting certain populations was their high peulustrin content. Another notable common property between some populations was the high umbelliprenin content in aerial plant parts. Some populations were clustered together due to their low overall coumarin content., (© 2016 Verlag Helvetica Chimica Acta AG, Zürich.)

Rhazya stricta Decne. (Apocynaceae) contains a large number of terpenoid indole alkaloids (TIAs). This study focused on the composition of alkaloids obtained from transformed hairy root cultures of R. stricta employing ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). In the UPLC-MS analyses, a total of 20 TIAs were identified from crude extracts. Eburenine and vincanine were the main alkaloids followed by polar glucoalkaloids, strictosidine lactam and strictosidine. Secodine-type alkaloids, tetrahydrosecodinol, tetrahydro- and dihydrosecodine were detected too. The occurrence of tetrahydrosecodinol was confirmed for the first time for R. stricta. Furthermore, two isomers of yohimbine, serpentine and vallesiachotamine were identified. The study shows that a characteristic pattern of biosynthetically related TIAs can be monitored in Rhazya hairy root crude extract by this chromatographic method.

Key Message: Transgenic hairy roots of R. stricta were developed for investigation of alkaloid accumulations. The contents of five identified alkaloids, including serpentine as a new compound, increased compared to non-transformed roots. Rhazya stricta Decne. is a rich source of pharmacologically active terpenoid indole alkaloids (TIAs). In order to study TIA production and enable metabolic engineering, we established hairy root cultures of R. stricta by co-cultivating cotyledon, hypocotyl, leaf, and shoot explants with wild-type Agrobacterium rhizogenes strain LBA 9402 and A. rhizogenes carrying the pK2WG7-gusA binary vector. Hairy roots initiated from the leaf explants 2 to 8 weeks. Transformation was confirmed by polymerase chain reaction and in case of GUS clones with GUS staining assay. Transformation efficiency was 74 and 83% for wild-type and GUS hairy root clones, respectively. Alkaloid accumulation was monitored by HPLC, and identification was achieved by UPLC-MS analysis. The influence of light (16 h photoperiod versus total darkness) and media composition (modified Gamborg B5 medium versus Woody Plant Medium) on the production of TIAs were investigated. Compared to non-transformed roots, wild-type hairy roots accumulated significantly higher amounts of five alkaloids. GUS hairy roots contained higher amounts two of alkaloids compared to non-transformed roots. Light conditions had a marked effect on the accumulation of five alkaloids whereas the composition of media only affected the accumulation of two alkaloids. By successfully establishing R. stricta hairy root clones, the potential of transgenic hairy root systems in modulating TIA production was confirmed.

Lignans from Schisandra chinensis berries show various pharmacological activities, of which their antioxidative and cytoprotective properties are among the most studied ones. Here, the first report on antibacterial properties of six dibenzocyclooctadiene lignans found in Schisandra spp. is presented. The activity was shown on two related intracellular Gram-negative bacteria Chlamydia pneumoniae and Chlamydia trachomatis upon their infection in human epithelial cells. All six lignans inhibited C. pneumoniae inclusion formation and infectious progeny production. Schisandrin B inhibited C. pneumoniae inclusion formation even when administered 8 h post infection, indicating a target that occurs relatively late within the infection cycle. Upon infection, lignan-pretreated C. pneumoniae elementary bodies had impaired inclusion formation capacity. The presence and substitution pattern of methylenedioxy, methoxy and hydroxyl groups of the lignans had a profound impact on the antichlamydial activity. In addition our data suggest that the antichlamydial activity is not caused only by the antioxidative properties of the lignans. None of the compounds showed inhibition on seven other bacteria, suggesting a degree of selectivity of the antibacterial effect. Taken together, the data presented support a role of the studied lignans as interesting antichlamydial lead compounds.

Introduction: Rhazya stricta Decne. (Apocynaceae) is a medicinal plant rich in terpenoid indole alkaloids (TIAs), some of which possess important pharmacological properties. The study material including transgenic hairy root cultures have been developed and their potential for alkaloid production are being investigated., Objective: In this study, a comprehensive GC-MS method for qualitative and quantitative analysis of alkaloids from Rhazya hairy roots was developed., Methods: The composition of alkaloids was determined by using GC-MS. In quantification, the ratio between alkaloid and internal standard was based on extracted ion from total ion current (TIC) analyses., Results: The developed method was validated. An acceptable precision with RSD ≤ 8% over a linear range of 1 to 100 µg/mL was achieved. The accuracy of the method was within 94-107%. Analysis of hairy root extracts indicated the occurrence of a total of 20 TIAs. Six of them, pleiocarpamine, fluorocarpamine, vincamine, ajmalicine and two yohimbine isomers are reported here for the first time in Rhazya. Trimethylsilyl (TMS) derivatisation of the extracts resulted in the separation of two isomers for yohimbine and also for vallesiachotamine. Clearly improved chromatographic profiles of TMS-derivatives were observed for vincanine and for minor compounds vincamine and rhazine., Conclusion: The results show that the present GC-MS method is reliable and well applicable for studying the variation of indole alkaloids in Rhazya samples., (Copyright © 2015 John Wiley & Sons, Ltd.)

We describe novel tools, bioluminescent whole-cell reporter gene assays, for facilitating the use of natural products in antimicrobial drug discovery. As proof-of-concept, a plant extract library was screened and follow-up experiments were carried out. Primary results can be obtained in 2-4h with high sensitivity, leading to significant improvements of the process., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the effect and selectivity of an extract of Schisandra chinensis berries against Chlamydia pneumoniae and C. trachomatis. Among the ethnopharmacological uses of the extract from Schisandrae fructus are cough and pneumonia. Therefore we focused on respiratory pathogens. The extract completely inhibited the growth of C. pneumoniae strain CV6 at 250 μg/mL concentration. The inhibition of C. pneumoniae and C. trachomatis growth was dose dependent and established with three different strains. The extract inhibited C. pneumoniae production of infectious progeny in a dose dependent manner. Chlamydia selectivity was elucidated with growth inhibition measurements of three other respiratory bacterial species. A pure compound found in Schisandra chinensis berries, schisandrin B at 20.0 μg/mL concentration inhibited the growth of both C. pneumoniae and C. trachomatis. The extract was found to be non-toxic to the human host cells. These findings highlight the potential of the extract from Schisandra chinensis berries as a source for antichlamydial compounds.

Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and control immune responses. Interferons, interleukins, and growth factors have applications in cancer, autoimmune, and viral disease treatment. The cytokines are susceptible to chemical and physical instability. This article reviews the structure and stability issues of clinically used cytokines, as well as formulation strategies for improved stability. Some general aspects for identifying most probable stability concerns, selecting excipients, and developing stable cytokine formulations are presented. The vast group of cytokines offers possibilities for new biopharmaceuticals. The formulation approaches of the current cytokine products could facilitate development of new biopharmaceuticals., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

The article reviews the present knowledge about brace treatment for adolescent idiopathic scoliosis (AIS). Indications, technique, problems, and results, are presented based on the literature. It is stressed by the authors that more scientific evidence is needed to reach a final conclusion whether brace treatment in AIS is effective or not.

The purpose of the present study was to compare the long-term clinical, functional and radiographic outcomes of young patients operated on before or at the onset of puberty (Children) and those operated on after that (Adolescents). The study group consisted of 298 patients operated on under the age of 20 years; 55 of them were operated on before or at the onset of growth spurt (29 females<12.5 years, 26 males<14.5 years). Preoperative data were retrieved from patients' records. After mean follow-up of 17 years (10.7-26.3), physical examination, radiographic measurements and functional testing were performed by independent observers. SRS-24, Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS) were utilised to evaluate health-related quality of life. The data were compared between the two age groups in the whole study population and in 41 pairs of patients matched by gender, operative method, severity of preoperative slip, and age at follow-up. Preoperatively, one-third of children did not have significant pain symptoms. They were operated upon for resistant postural anomalies in combination with high risk of slip progression. All of the adolescents had low-back pain as the main clinical symptom. The outcomes were satisfactory in both groups in the whole population (children vs. adolescents; low-grade slip: SRS-24: 95.9 vs. 92.0, ODI: 5.2 vs. 7.5, VAS low-back pain: 18.9 vs. 21.2; high-grade slip: SRS-24: 95.6 vs. 90.6, ODI: 3.4 vs. 6.9, VAS low-back pain: 10.5 vs. 22.1). The differences were statistically significant for ODI and VAS in high-grade patients in favor of the children. The clinical relevance of these differences seems to be minimal. The results of the comparison of the matched cohorts were comparably good. One-fifth of the whole study group had a non-union which did not affect the final outcome. In the children with high-grade slips, there was a mean slip improvement of 14 percentage points due to remodelling. The overall complication rate in the whole population was 7.7%. In conclusion, spinal fusion can be carried out at an early age for low- and high-grade spondylolisthesis with good long-term clinical, functional, radiographic and health-related quality-of-life outcomes when the indications are met.

The aim of the study was to compare the results of brace treatment of adolescent idiopathic scoliosis (AIS) in male patients with matched female patients and to assess the effectiveness of bracing of boys in AIS and to discuss the results with published data. Between 1987 and 1995, 51 consecutive male patients with AIS were treated with the Boston brace. The patients were advised to wear the brace 23 h/day. The medical records of all patients were reviewed. Cobb angles and Risser signs were measured before bracing, in brace, at brace discontinuation and at final follow-up. Everyone of 51 male patients was compared with a female patient who was treated by the same method and matched by Risser sign, curve pattern, curve magnitude and duration of treatment and follow-up time. Compliance with brace was noted at every visit. Fourteen boys had worn the brace only during nighttime or occasionally and were considered non-compliant. Only compliant patients with treatment period > 1 year and follow-up > 1 year after treatment were accepted for the analyses of effectiveness of brace treatment and its prognostic factors. Thirty-three boys met these inclusion criteria. Bracing was considered to have a failure if > 5 degrees progression occurred or if surgery was performed. At the final follow-up study progression > 5 degrees was found in 16/51 (31.4%) of male patients. Corresponding figures of female patients were 11/51 (21.6%), respectively. In compliant boys progression > 5 degrees occurred in 6/33 boys compared with 9/33 girls. The association between risk of progression and correction% in brace was statistically significant. The overall results of brace treatment of idiopathic scoliosis in male patients were inferior compared with matched females. One reason for inferior overall results in boys was poor compliance with brace wear. However, brace treatment in AIS may be recommended with the same principles in both genders.

The aim of the present study was to assess the long-term clinical, functional, and radiographic outcome of direct repair of spondylolysis using cerclage wire fixation according to Scott in young patients with symptomatic spondylolysis or low-grade isthmic spondylolisthesis as compared to the outcome after uninstrumented posterolateral in situ fusion. Twenty-five out of 28 patients of the direct repair group (89%) and 23 out of 28 of the fusion group (82%) were available for follow-up examination. The assessment by independent observers included a structured interview (Oswestry questionnaire [ODI], visual analogue scale, SRS questionnaire), a clinical examination, functional testing, plain radiography, and MRI. The groups were comparable as to the mean age at operation (18.2 vs. 16.2 years.), the follow-up time (14.8 vs. 15.0 years), and the amount of preoperative slip (7.2 vs. 13.1%). The mean ODI and SRS total scores were significantly better in the fusion group (4.3 [0-16] and 96 [57-117]) as compared to the direct repair group (11.4[0-52] and 87[53-107]; P=0.02 and P=0.011, respectively). In functional testing, both groups reached normal values for abdominal and back muscle strength. The lumbar spine flexion and extension ROM was decreased in both groups showing no statistical difference between the groups. Significant progressive narrowing of the olisthetic disc was detected on the plain radiographs after direct repair. On the flexion-extension radiographs, in the direct repair group, the mobility in the lytic/olisthetic segment was decreased in comparison to normal values from the literature. The mobility at the level above the operated segment was decreased in the direct repair group as compared to the fusion group (P=0.057). On T2-weighted MR images in the direct repair group, the signal intensity of the disc below the affected vertebra was decreased in 17/23 (74%) patients. There was no difference between the groups in the nucleus signal intensity of the adjacent disc above the operated segment. No association between the disc degeneration on MRI and the outcome of the patients could be established. In the direct repair group the following complications were seen: transient nerve root irritation (2), superficial infection (1), UTI (1); in the fusion group the complications were: subcutaneous seroma (2) and UTI (1). There were six re-operations, cerclage removal(4), conversion into segmental fusion(2) in the direct repair group, and one re-operation, instrumented respondylodesis, in the fusion group. In conclusion, the results of direct repair of the spondylolysis using cerclage wire fixation according to Scott were very satisfactory in 76% of the patients after a mean follow-up of 14.8 years. After direct repair, the ODI deteriorated with time leading to a clinically moderate but statistically significant difference in favour of segmental fusion. Lumbar spine mobility was decreased after direct repair. Secondary segmental instability above the spinal fusion was not detected. The procedure does not seem to be capable of preventing the olisthetic disc from degeneration. The theoretical benefits of direct repair could not be proven.

Study Design: A cross-sectional study to evaluate the long-term result of posterolateral (PLF), anterior (AF), and circumferential fusion (CF) for isthmic spondylolisthesis., Objectives: To assess the long-term effects of PLF, AF, or CF for high-grade isthmic spondylolisthesis on lumbar spine in children and adolescents by using MRI., Summary of Background Data: Short- and mid-term clinical and plain radiographic results of isthmic spondylolisthesis and of PLF, AF, and CF in severe slip are well documented. The long-term effect of the fusion on soft tissues, on the intervertebral discs inside and above fusion in particular, is, however, unclear., Methods: Between 1977 and 1991, PLF (n = 21), AF (n = 22), or CF (n = 24) was performed on 67 patients (42 females, 25 males) with high-grade (slip > or =50%) isthmic spondylolisthesis. The average age of patients at the time of operation was 14.4 (range, 8.9-19.6) years. Clinical, spinal mobility and trunk strength in addition to MRI and plain radiograph examinations were performed on these patients after an average follow-up time of 17.3 years (range, 10.7-26.0 years)., Results: Three (14%) patients in the PLF and AF groups, but none in the CF group, reported back pain often or very often at rest. The mean Oswestry Disability Index (ODI) was 9.7 (range, 0-62) in the PLF, 8.1 (0-32) in the AF, and 2.3 (0-14) in the CF group (P < 0.05). The mean slip before surgery was 66% (range, 50%-100%) and at the last follow-up visit 66% (range, 26%-106%). Disc degeneration was most common in the PLF group (P = 0.0014) and inside the fusion and in the lowest moving intervertebral disc spaces in all subgroups. Only 1 patient had an asymptomatic prolapse. In MR images, none of the patients had lumbar central canal stenosis inside or above the fusion. In contrast, the spinal canal was wide at the spondylolysis and spondylolisthesis level in 23 (34%) patients. Of the patients, 19 (28%) patients (32 neural foramens) had severe narrowing of the neural foramen with impingement of the nerve root. No patients had clinically confirmed L5 nerve root symptoms. Muscle degeneration was found in 29 (43%) of patients. Longer fusion and muscle degeneration, but not disc degeneration, were associated with lower performance in spinal mobility and trunk-strength measurement tests., Conclusions: The clinical outcome was best in the CF group as measured by ODI. Degenerative changes were most commonly found at the level of the slip and above the fusion level. The prevalence of disc prolapses was low. Spinal fusion for isthmic spondylolysis is not associated with central canal stenosis above the fusion. Radiologic nerve root stenosis was common but asymptomatic. Mild muscle atrophy was common.

Growth velocities, curve magnitudes, curve patterns and Risser signs of 80 consecutive untreated boys with adolescent idiopathic scoliosis were studied retrospectively and compared with the progression velocity of the curves. Growth velocity >or=4 cm/year with curves >or=25 degrees increased progression velocity of curves significantly (P<0.001). Growth velocity was fastest at skeletal ages 12-13 years but continued moderately after the age of 16 years. The major right thoracic curves were the most progressive.

The aim of the study was to assess the results of treatment of adolescent idiopathic scoliosis (AIS) with the Providence nighttime brace at 1.8 years after discontinuation of bracing. A total of 36 consecutive female patients with an average Cobb angle of 28.4 degrees and an apex below T 10 were studied prospectively. For comparisons, 36 matched patients treated with the Boston full-time brace were studied retrospectively. With the Providence night brace an average of 92% for brace correction of the primary curve was achieved and during follow-up progression of the curve >5 degrees occurred in 27% of the patients. In the control group of the Boston full-time brace patients, brace correction was 50% and the progression of the major curve occurred in 22% of the patients. We conclude that the Providence night brace may be recommended for the treatment of AIS with curves less than 35 degrees in lumbar and thoracolumbar cases.

Study Design: Retrospective follow-up study with two cohorts: one treated with reduction and the other with fusion in situ., Objective: To assess the long-term effects of reduction versus fusion in situ on lumbar spine in children and adolescents with severe L5 isthmic spondylolisthesis., Summary of Background Data: Severe isthmic spondylolisthesis is commonly treated with fusion in situ, but modern surgical techniques and instrumentation permit the reduction of a severely slipped fifth lumbar vertebra. Advocates of one or another of these procedures present different claims to defend their choice. However, to our knowledge, no long-term results of the reduction maneuver exist., Methods: Between 1983 and 1991, 22 adolescents with severe (more than 60%) slip were treated surgically. In 11 of them, reduction was performed with a Magerl/Dick transpedicular device, followed by fusion posteriorly from L4 or L5 to S1 and anteriorly from L5 to S1. In the others, fusion was performed in situ posteriorly from L4 (n = 7) or L5 (n = 4) to S1 and anteriorly from L5 to S1. The average age of patients at surgery was 14.7 years (range 10.7-18.5). Radiographs obtained before surgery, after surgery, and at the final follow-up evaluation were assessed for quality of fusion. In addition, magnetic resonance imaging was obtained at the last follow-up visit. Average follow-up time was 14.8 years (range 11.6-18.7). Physical examination, spinal mobility, and nondynamometric trunk strength measurements were used to assess, and Oswestry Disability Index and Scoliosis Research Society scores were used to calculate outcome at the last follow-up visit., Results: In the reduction group, mean Oswestry Disability Index was 7.2 (range 0-20) and in the fusion in situ group, was 1.6 (range 0-4) (P = 0.0096). The Scoliosis Research Society total score averaged 90.0 (range 39-107) in the reduction group and 103.9 (range 93-120) in the fusion in situ group (P = 0.046). At the last follow-up evaluation, mean vertebral slip had decreased from the preoperative value of 90% to 57% in the reduction group but remained the same (80% vs. 78%) in the fusion in situ group (P = 0.04 and 0.013, respectively, for preoperative and postoperative comparison). On magnetic resonance imaging, disc degeneration above the fusion was more common in the reduction group (P = 0.004). None of the patients had spinal stenosis above the fusion. Nerve root canal impingement at the L5-S1 level was more common in the fusion in situ group (P = 0.03), but all patients were free of L5 nerve root symptoms. There was no difference in spinal mobility or trunk strength measurements between the groups., Conclusions: The fusion in situ group seems to perform better in almost all clinical parameters measured. These findings suggest that fusion in situ should be considered as a method of choice in severe L5 isthmic spondylolisthesis.

Study Design: A retrospective, comparative follow-up study., Objective: To compare clinical and radiographic outcomes after posterolateral, anterior, or circumferential fusion in situ for high-grade spondylolisthesis in children and adolescents., Summary of Background Data: Controversial opinions still exist about the surgical treatment of severe isthmic spondylolisthesis. There are no long-term comparative studies of different fusion in situ techniques in these patients., Methods: A total of 21 patients treated using posterolateral, 23 using anterior, and 26 using the circumferential fusion technique without instrumentation for high-grade isthmic spondylolisthesis (>or=50% slip) participated. Their mean age at surgery was 14.4 years (range 8.0-19.6). The follow-up rate was 84% after a mean of 17.2 years (range 10.7-26.0). Radiographs were obtained before surgery, at 2-year follow-up, and at final follow-up. The Scoliosis Research Society (SRS) and Oswestry Disability Index questionnaires were completed, and a physical examination was performed at the final follow-up visit., Results: Progression of lumbosacral kyphosis (>or=10 degrees ) was found in 9 (43%), 3 (13%), and 3 (12%) patients of the posterolateral, anterior, and circumferential fusion groups, respectively (P = 0.017). The SRS total score averaged 89.7 (range 56-105) in the posterolateral, 93.2 (range 66-114) in the anterior, and 100.0 (range 71-117) in the circumferential fusion groups (P = 0.021). Patients in the circumferential fusion group had better values for pain (P = 0.023) and function from back condition domains (P = 0.079) than patients in the posterolateral or anterior groups. The Oswestry Disability Index averaged 9.7 (range 0-62) in the posterolateral, 8.9 (range 0-32) in the anterior, and 3.0 (range 0-16) in the circumferential fusion groups (P = 0.035)., Conclusions: Circumferential fusion provided significantly better long-term clinical, radiographic, and SRS total score than posterolateral or anterior fusion for high-grade isthmic spondylolisthesis.

Between 1977 and 1987, posterior (n=29) or posterolateral (n=73) fusion was performed for mild to moderate (slip <50%) isthmic spondylolisthesis on 102 patients (46 females, 56 males). The patients' average age at the time of operation was 15.9 (range, 8.1-19.8) years. Clinical (physical examination and Oswestry disability index (ODI)) and radiological (MRI and plain radiographs) examinations were performed on these patients after an average follow-up time of 21.0 (range, 26.2-15.1) years. In the radiographs, the mean slip preoperatively was 27% (range, 5-50%) and at the last follow-up visit 26% (range, 5-78%). Inside the fusion, there were a total of 148 intervertebral discs, 121 (82%) of them had decreased signal intensity in T2-weighted MR images and 113 (76%) were narrowed. Above the fusion level, 27 (27%) discs were speckled and 27 (27%) were black; 21 (21%) intervertebral disc spaces were narrowed. Two levels above the fusion level the numbers were 8 (8%), 16 (16%) and 16 (16%), respectively. Six (6%) patients had a prolapse. Degenerative facet joint hypertrophy above fusion was seen at 80 (79%) of the levels studied. When compared to healthy subjects higher frequency of disc and facet joint degeneration was found. In MR images, none of the patients had lumbar spinal stenosis inside or above the fusion. Narrowing of one or both of the neural foramina at the level of the L5-S1 interververtebral disc was noted in 32 (31%) patients. Seventeen (17%) of the patients had, usually mild, muscular atrophy of the psoas and 33 (32%) of the paraspinal muscles. There was no difference in frequency of abnormal MRI findings between patients (n=93) with ODI 20 or less compared with patients (n=9) with ODI more than 20. In situ fusion due to isthmic spondylolsthesis at adolescence is associated with moderate degenerative changes in the lumbar spine during a 20-year follow-up. Changes were most commonly found at the level of the spondylolisthesis and above fusion level. Neural foramina stenosis seems to be associated with spondylolisthesis and its severity to severity of the slip. Muscle atrophy tended to be mild. However, there was no correlation between patient outcome (ODI) and abnormal lumbar MRI findings.

Study Design: A retrospective follow-up study comparing 2 matched groups., Objective: To compare long-term results of operative treatment of adolescent idiopathic scoliosis (AIS) between males and females matched for age, curve magnitude and type, and the instrumentation used., Summary of Background Data: It has been suggested that in AIS, the spine is more rigid in males than in females, because brace treatment fails to halt progression of the curves in males. However, there are no studies comparing the results of surgical treatment of AIS between males and females., Methods: Thirty male and female pairs were matched for age (+/-1 year), major curve magnitude (+/-5 degrees), curve type according to the King classification, and the instrumentation used (Harrington in 11 pairs, Cotrel-Dubousset in 9 pairs, and Universal Spine System in 10 pairs). The mean age at the time of operation was 16.2 +/- 2.6 years for the males and 15.5 +/- 2.3 years for the females. The mean follow-up times were 14.3 years (range 6.7-23.0 years) and 14.1 year (range 6.4-23.7 years), respectively. Radiographs were obtained presurgery and after surgery, at the 2-year follow-up assessment, and at the final follow-up visit. In addition, a physical examination was performed, and the Scoliosis Research Society (SRS) questionnaire was completed. Spine mobility and nondynamometric trunk strength were measured at the final follow-up visit., Results: Before surgery, the mean Cobb angle of the thoracic curve was 55 degrees (range 42-83 degrees) in the males and 56 degrees (range 43-80 degrees) in the females. In bending radiographs, the major curve reduced significantly more in females than in males (P = 0.027). The mean angles of the thoracic and lumbar curves were similar at all follow-up visits. The final correction of the thoracic curves was 30% (range -19-65%) in the males and 33% (range -7-71%) in the females (not significant). No significant difference was observed in thoracic kyphosis or lumbar lordosis between the study groups at the final follow-up. The total SRS questionnaire score averaged 96 (range 66-113) in the males and 95 (range 75-108) in the females. None of the males and 2 of the females reported back pain often or very often in the questionnaire. Nondynamometric trunk strength measurements corresponded with reference values, on average, and were similar in both groups. Abnormal trunk side bending tended to be more common in the males than in the females (43% vs. 23%, P = 0.10, not significant)., Conclusions: Curves in males appear to be more rigid than in females with AIS. However, posterior surgery for AIS provides similar short and long-term results in males and females.

Study Design: A retrospective follow-up study of low-grade (slip < or = 50%) isthmic spondylolisthesis after posterior or posterolateral fusion in young patients., Objective: To evaluate the usefulness of the Scoliosis Research Society questionnaire and compare it with Oswestry Disability Index and radiographic parameters in patients with isthmic spondylolisthesis., Summary of Background Data: A few studies have examined long-term patient outcome using validated questionnaires or compared it with radiographic parameters after surgery for isthmic spondylolisthesis in young patients. The Scoliosis Research Society questionnaire provides patient-oriented information on back pain, cosmetic aspects, patient satisfaction, and level of activity and might therefore be suitable for evaluation of surgical outcome after isthmic spondylolisthesis in young patients. However, there are no studies assessing the usefulness of the Scoliosis Research Society questionnaire for these patients., Methods: One hundred and eight patients treated at a mean (range) age of 15.9 (range, 8.1-19.8) years with posterior (n = 29) or posterolateral (n = 79) in situ fusion for isthmic spondylolisthesis participated in the present study. The follow-up rate was 83% after a mean of 20.8 (range, 15.1-25.9) years. The mean age at follow-up observation was 36.7 years. Radiographs were obtained before surgery, at 2-year follow-up observation, and at final follow-up review. The Scoliosis Research Society and Oswestry Disability Index questionnaires were completed, and a physical examination was performed at the final follow-up visit., Results: Nonunion after primary operation was found in 10 (34%) patients after posterior fusion and in 10 (13%) patients after posterolateral fusion (P = 0.0017). The mean (range) anterior slip was 25.2% (0-50%) before surgery and 24.2% (0-78%) at final follow-up observation. Lumbosacral kyphosis increased significantly during the follow-up period. The Scoliosis Research Society questionnaire yielded a total of 94.0 (range, 44-114) points. On the Scoliosis Research Society questionnaire, 14 (14%) patients reported back pain often or very often at rest. The Oswestry Disability Index scores averaged 8.2 (range, 0-68). There was a significant correlation between the Scoliosis Research Society total score and the Oswestry Disability Index. The percentage slip showed significant inverse correlations with the scores for appearance in clothes, attractiveness, and self image (Scoliosis Research Society questions 5, 14, and 15)., Conclusions: Long-term clinical and radiographic outcomes after posterolateral fusion of low-grade spondylolisthesis were satisfactory. Cosmetic aspects of this deformity should be included as one of the outcome measurements, since cosmetic questions on the Scoliosis Research Society questionnaire showed inverse correlations between the amount of slip at final follow-up observation. The Scoliosis Research Society questionnaire could be used as a primary patient-oriented outcome tool after back surgery in young patients.

Study Design: A retrospective comparison of the clinical, radiologic, and functional results of Cotrell-Dubousset (CD) and Universal Spine System (USS) instrumentation for adolescent idiopathic scoliosis (AIS)., Objectives: To establish whether there are any differences in outcome between the 2 instrumentation systems., Summary of Background Data: CD is the first complex posterior double rod instrumentation system to provide multiple hook fixation. USS instrumentation permits the use of rod translation instead of rod rotation, the option to secure pedicle hooks with fixation screws, and the option to use transpedicular screws in the lower thoracic and lumbar spine. Midterm and long-term results of USS instrumentation are lacking., Methods: Fifty-seven (mean age, 28 years at follow up) patients treated with CD instrumentation and 55 (mean age, 23 years at follow up) patients treated with USS instrumentation for AIS participated in the study. The average follow-up rate was 80% and time 13.0 years for the CD group, and 95% and 7.8 years for the USS group. Radiographs were obtained before surgery, at 2-year follow up, and at final follow up. Additionally, a physical examination was performed by 2 independent observers, and the Scoliosis Research Society (SRS) questionnaire was completed; spinal mobility and nondynamometric trunk strength were measured at the final follow-up visit. RESULTS.: The mean Cobb angle of the instrumented thoracic curve was before surgery 55 degrees (range, 36-83 degrees for the CD and 52 degrees (range, 35-85 degrees) for the USS group. The mean number of instrumented vertebrae was 9.9 (range, 7-12) in the CD and 9.8 (range, 6-12) in the USS group. At final follow up, the mean angles were 32 degrees (range, 13-63 degrees) for the CD group and 29 degrees (range, 9-63 degrees) for the USS group (not significant). No significant difference was observed in thoracic kyphosis or lumbar lordosis between the study groups at final follow up. In the SRS questionnaire, the total score averaged 97 for the CD and 101 for the USS groups, respectively. In the questionnaire, 6 (11%) patients in the CD group, but none in the USS group, reported having low back pain often or very often at rest. No correlation was found between the Cobb angle of the thoracic or lumbar curves at follow up and the total score or back pain indexes of this questionnaire. Nondynamometric trunk strength measurements corresponded with age- and sex-adjusted reference values, on average, but patients in the CD group performed significantly better in the squatting test (P = 0.021) and patients in the USS group performed better in trunk side bending (P = 0.004). Complications were recorded in 15 (26%) patients in the CD and in 13 (24%) patients in the USS group (not significant)., Conclusions: The midterm radiologic and functional outcomes were quite similar in both groups as were the SRS scores. The patients performed, on average, as well as did the reference population in nondynamometric trunk strength measurements. Intraoperative and late complications were similar in both groups.

Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P < 0.05) and the MPS diet by 35% (P < 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rapeseed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.

Body mass index (BMI) as a predictor of slipped capital femoral epiphysis (SCFE) was studied. A total of 26 adolescent patients had complete annual height and weight measurements taken from birth to onset of slippage. These values were compared with those of the normal adolescent population. Patients with SCFE showed statistically higher BMI during growth than normal developing children. BMI gives more accurate data on body build than height and weight alone and may be a useful tool for evaluating risk factors in SCFE.

A method for the separation of parasorboside and gerberin from the ornamental plant Gerbera hybrida (Asteraceae) has been developed. The two closely related glucosides were extracted using an Extrachrom instrument, a prototype multi-functional separation tool equipped with an extraction chamber. The rotation planar extraction procedure was compared with that of a medium pressure solid-liquid extraction system. The resulting extracts were pre-purified using rotation planar chromatography and the results compared with those obtained using medium pressure liquid chromatography with silica gel as the stationary phase and a mobile phase of methanol:ethyl acetate:tetrahydrofuran at selectivity point Ps = 111 with 1% formic acid as modifier. The title compounds were isolated from the purified extracts by TLC and their structures confirmed by 1H- and 13C-NMR spectroscopy.

Study Design: A retrospective follow-up study of adolescent idiopathic scoliosis after Harrington instrumentation and spondylodesis was conducted., Objective: To correlate radiographic parameters with the Scoliosis Research Society questionnaire in terms of patient outcome, clinical findings, spine mobility, and trunk strength measurements., Summary of Background Data: Previous studies have shown that long-term radiologic correction can be achieved with Harrington instrumentation. It seems, however, that radiologic correction does not correlate with patient outcome. There are no previous studies on long-term results of functional outcome, including spine mobility and trunk strength measurements, after operative treatment of adolescent idiopathic scoliosis, as compared with findings in the normal population., Methods: Of 98 consecutive patients who underwent surgery with Harrington distraction rod and posterior spondylodesis in 1979, 78 (80%) (11 males; mean age, 36 years) participated in the study. The average follow-up period was 20.8 years (range, 19.1-22.4 years). Radiographs were obtained before surgery, at the 2-year follow-up assessment, and at the 20-year follow-up assessment. Additionally, physical examination was performed, and the Scoliosis Research Society questionnaire was completed. Spine mobility and nondynamometric trunk strength measurements were obtained at the 20-year follow-up assessment., Results: The mean Cobb angle of the instrumented thoracic curve was 53 degrees +/- 10 degrees before surgery, and 38 degrees +/- 11 degrees at the 2-year follow-up assessment. At the 20-year follow-up assessment, the mean angle was 45 degrees +/- 12 degrees. Degenerative changes in the noninstrumented lumbar spine (sclerosis of facets, endplate sclerosis, osteophyte formation) were noted in 17 patients (22%). Ten patients (13%) reported having low back pain often or very often at rest according to the Scoliosis Research Society questionnaire. No correlation was found between the Cobb angle of the thoracic or lumbar curves at follow-up assessment and the Scoliosis Research Society total score or back pain indexes. Neither was any association found between the Scoliosis Research Society total score and the spondylodesis fusion level. However, the magnitude of the thoracic curve at follow-up assessment showed a significant inverse correlation with the scores for Scoliosis Research Society questions about cosmetic aspects. The nondynamometric trunk strength measurements corresponded with the reference values, on the average, but did not show any correlation with the magnitude of the thoracic or lumbar curves or with the Scoliosis Research Society total score or back pain indexes. Spine mobility, especially trunk side bending, was diminished in 59% of the patients, and did not correlate with the Scoliosis Research Society total score or individual indexes., Conclusions: In patients with adolescent idiopathic scoliosis who undergo surgery with Harrington instrumentation, the overall long-term clinical outcome does not correlate with the radiologic outcome. However, a significant inverse correlation was found between the magnitude of the primary thoracic curve at follow-up assessment and the scores for questions on cosmetic matters in the Scoliosis Research Society questionnaire. Spine mobility is diminished as a result of spondylodesis, but the patients perform, on the average, as well as the normal population in nondynamometric trunk strength measurements.

In the literature, long-term prognosis of Legg-Calvé-Perthes disease (LCPD) means prognosis for secondary osteoarthritis of the hip joint or leg-length inequality and its consequences. Most studies show results after conservative treatment. The long-term natural history of LCPD is not known. In spite of deformity, most patients do well in early adulthood. Radiographic and clinical osteoarthritis is increased in 20-year to 40-year follow-ups and degenerative joint disease develops in the majority of patients by the sixth or seventh decade of life. The reported average shortening of the affected leg has usually been 1 to 1.5 cm. There are no thorough long-term reports on low back pain after LCPD. The only evidence-based factors that are of prognostic importance in the long-term are age of the patient at the onset of the disease and shape of the femoral head at skeletal maturity.

The prognosis of Perthes' disease was studied after femoral intertrochanteric varus osteotomy in 112 patients (126 hips) and after conservative noncontainment treatment (Thomas splint) in 96 patients (106 hips). The radiographic results at or near skeletal maturity after containment treatment were good in 45%, fair in 21%, and poor in 34% of the hips. The figures after noncontainment treatment were 21%, 18% and 61%, respectively. The results support the idea that containment of the femoral head in the acetabulum should form the basis of treatment for Perthes' disease. It was very difficult to delineate signs for good prognosis; age at onset of the disease and a good containment three months postoperatively in the operatively treated group were the only signs with prognostic significance. In both groups, one fifth of the patients had an extremely poor outcome. Treatment other than varus osteotomy or noncontainment treatment should be considered in these patients.

A follow-up of 96 patients with Perthes' disease was made 28-47 years after onset of the disease. We paid special attention to leg-length inequality and its consequences and low-back disability. Leg-length inequality was a common finding, but low-back pain was not a significant problem. Leg-length inequality and lumbar scoliosis correlated poorly with low-back disorders. Degeneration of the lumbar spine was the only factor that correlated well with low-back pain.

The results in 96 patients (106 hips) with Perthes' disease who had had conservative noncontainment treatment were studied after 35 (28-47) years. At skeletal maturity, the radiographic result was poor in 65 hips. At the average age of 43 years, radiographic signs of arthrosis were found in 48 patients (51 hips); 5 patients had had hip replacement and 13 patients had symptoms justifying that procedure. At early phases of the disease, radiographs showed biocompartmentalization of the acetabulum in 24 percent of the hips, but the acetabulum normalized in the majority. There was no difference in long-term prognosis between Catterall's Groups III and IV; two or more signs of head-at-risk were not of prognostic value. The patients' age at diagnosis and the shape of the femoral head at skeletal maturity were the most reliable prognostic factors.

We analyzed clinical and radiographic long-term results in 96 patients (106 hips) with Perthes' disease 35 years after nonoperative treatment. 19 hips in 17 patients had early radiographic signs indicating atypically severe course of the disease and poor prognosis. None of them was radiographically good at skeletal maturity; 2 cases were fair and 17 poor. At the final follow-up 12 hips had radiographic arthrosis.

We analyzed various prognostic factors in 112 children operated on for Perthes' disease (Catterall's groups II-IV); special attention was paid to acetabular changes and postoperative containment. The radiographic results of 126 intertrochanteric femoral varus osteotomies were analyzed 2-16 years postoperatively. Catterall's grouping or head-at-risk phenomenon, bicompartmentalization of the acetabulum, and preoperative subluxation of the femoral head did not correlate with the result. The result was worse in cases operated on in the healing phase of the disease and in patients operated on at the age of 9 years or older. The strongest prognostic factor was containment of the femoral head after osteotomy.

In 52 patients 0.5-3.0 ml of iohexol, 180 mg/ml, was injected using lateral injection technique and fluoroscopy control. A total of 146 lumbar discs using local anaesthesia was injected. Two types of premedication were used; either diazepam alone or diazepam in combination with pethidine and glycopyrronium bromide. There was no difference in the discography injection pain between the groups (X2 = 0.774, P greater than 0.05]. During discography, some patients had nausea (2%), convulsions (4%), back pain (6%) and hypotension (10%), but no allergic reactions were seen. This suggests that these immediate reactions are more related to the procedure itself than to the non-ionic ratio 3.0 iohexol contrast medium. More troublesome iatrogenic complications were seen the day after the discography in the form of severe headache (10%) probably related to liquor leakage, and increasing low back pain (81%). The latter may be caused by local haematoma or chemical irritation from iohexol. Patients with no pain during injection had a relatively slight need for analgesics (Somer's D = -0.196, P less than 0.05).

A total of 126 Perthes diseases (112 patients) were studied. The treatment comprised intertrochanteric femoral varus osteotomy in every patient. In 20 patients (25 hips), the course of the disease was more severe than expected. The early radiological criteria for this severe course were: 1. Lateral calcification extending far laterally towards the greater trochanter, 2. Deformation and widening of the femoral head before the fragmentation phase, 3. The Saturn phenomenon; a sclerotic epiphysis surrounded by a ring of looser bony tissue, 4. Deformation and widening of the femoral neck at the initial phase of the disease, 5. Early wide sclerotic changes in the metaphysis. The overall results were poor. Two hips obtained a fair and 23 poor results. These described radiological changes are readily recognized at early phase of Perthes disease and indicate poor prognosis. In these cases varus osteotomy gave unsatisfactory results which means that other type of treatment in these patients should be considered.

Two different classifications of discograms have been used in a prospective study of 279 injected discs in 100 patients. The five-stage classification of Adams, Dolan and Hutton (1986) showed increased degeneration in the lower lumbar discs and more degenerative changes in men than in women. Exact reproduction of the patient's pain on injection was more common in fissured or ruptured discs than in less degenerate discs, with 81% sensitivity and 64% specificity of the discogram for pain. The additional information obtained by comparing computerised tomography (CT) with discograms was minimal. Discography was found to be useful in the evaluation of chronic low back pain in patients whose ordinary CT scans, myelograms and flexion-extension radiographs were normal. In spondylolysis and spondylolisthesis, discography can disclose whether fusion needs to be extended above the lytic level, and it may show if the pain in patients who have had posterolateral fusion is discogenic. Thus, discography gives information which is useful in deciding whether to operate on patients with chronic low back pain.