Archive of Medical Research

The metal-binding features of the recombinant mussel Mytilus edulis MT-10-IV metallothionein.

In contrast with the paradigmatic mammalian metallothioneins (MTs), mollusc MT systems consist at least of a high-cadmium induced form, possibly involved in detoxification, and another isoform either constitutive or regulated by essential metals and probably associated with housekeeping metabolism. With the aim of providing a deeper characterization of the coordination features of a molluscan MT peptide of the latter kind, we have analyzed here the metal-binding abilities of the recombinant MeMT-10-IV isoform of Mytilus edulis (MeMT). Also, comparison with other MTs of this type has been undertaken. A synthetic complementary DNA was constructed, cloned and expressed into two Escherichia coli systems. Upon zinc coordination, MeMT folds in vivo into highly chiral and stable Zn(7) complexes, with an exceptional reluctance to fully substitute cadmium(II) and/or copper(I) for zinc(II). In vivo cadmium binding leads to homometallic Cd(7) complexes that structurally differ from any of the in vitro prepared Cd(7) complexes. Homometallic Cu-MeMT can only be obtained in vitro from Zn(7)-MeMT after a great molar excess of copper(I) has been added. In vivo, two different heterometallic Zn,Cu-MeMT complexes are recovered, which nicely correspond to two distinct stages of the in vitro zinc/copper replacement. These MeMT metal-binding features are consistent with a physiological role related to basal/housekeeping metal, mainly zinc, metabolism, and confirm the correspondence between the MeMT gene response pattern and the functional properties of the encoded protein.

Orihuela R, Domènech J, Bofill R, You C, Mackay EA, Kägi JH, Capdevila M, Atrian S.

Departament de Química, Facultat de Ciències, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.

Spinal synovial cysts: pathogenesis, diagnosis and surgical treatment in a series of seven cases and literature review.

This study is designed based on the retrospective analysis of patients treated in the Neurosurgical Department of two major hospitals and review of the literature. The aim of this study is to evaluate the efficacy of surgery and address controversial issues in the treatment of symptomatic lumbar intraspinal synovial cysts. Spinal juxtafacet cysts (synovial and ganglion cysts) are a rare cause of low back and radicular leg pain. Although the relevant reports in the international literature are increasing, the controversy about conservative versus surgical treatment and the need for concomitant fusion still exists. Data from seven patients (age range 58-69 years, mean age 61 years) with low back and radicular leg pain due to a lumbar facet joint cyst were retrospectively analyzed. Demographic data, cyst level, presence of concomitant local pathology, treatment and results of treatment were recorded. A follow-up of at least 6 months (range 6-48 months) was conducted and results were noted. All patients had back pain, while five also experienced unilateral radicular leg pain and one had bilateral leg pain. One patient had neurogenic claudication. MRI identified the cyst and highlighted underlying pathology in all cases. All patients underwent surgical cyst excision. No fusion was performed. Post-operatively, all patients showed a total resolution of symptoms with sustained benefit at final evaluation. Review of the literature revealed a trend towards surgery, as this is correlated to a more favorable outcome compared with conservative treatment. Fusion should be performed on a case-by-case basis only. Surgery is a safe and effective treatment choice in this increasingly appearing ailment. A prospective, randomized trial should clarify issues under debate.

Boviatsis EJ, Staurinou LC, Kouyialis AT, Gavra MM, Stavrinou PC, Themistokleous M, Selviaridis P, Sakas DE.

Department of Neurosurgery, University of Athens Medical School, Evangelismos General Hospital, 61 Ipsilantou Street, Athens, 115 21, Greece, eboviats@med.uoa.gr.

Donor site morbidity following iliac crest bone harvesting for cervical fusion: a comparison between minimally invasive and open techniques.

We have studied the occurrence of donor site morbidity, cosmesis and overall satisfaction with graft procedure in 76 patients who had undergone iliac crest bone harvesting for anterior cervical discectomy and fusion (ACDF). Totally 24 patients underwent an open procedure and 52 a minimally invasive trephine harvesting method. Although our study demonstrated substantial donor site pain and its effect on ambulation in both groups, this was of limited duration. Two patients, one in each group, suffered long-term pain that was eventually resolved. Totally 8.3% of patients in the open group suffered minor complications and 11.5% in the trephine group. There were two cases of meralgia parasthetica. There were no major complications in either group. There was no statistically significant difference in morbidity between the open and trephine groups. There was a trend towards significance (P = 0.076) for pain at the donor site, with less pain reported by patients who underwent the trephine procedure for harvesting.

Pollock R, Alcelik I, Bhatia C, Chuter G, Lingutla K, Budithi C, Krishna M.

Spinal Unit, University Hospital of North Tees, Stockton on Tees, TS19 8PE, UK.

Comments about \”European guidelines for the diagnosis and treatment of pelvic girdle pain\”

Nordin M.

Departments of Orthopaedics and Environmental Medicine, Program of Ergonomics and Biomechanics, School of Medicine and Graduate School of Arts and Science, New York University, New York, NY, USA, margareta.nordin@nyu.edu.

Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients.

A case-control study was conducted to examine the association between two single nucleotide polymorphisms (SNPs) in exon 2 of the bone morphogenetic protein-2 gene (BMP-2) and ossification of the posterior longitudinal ligament (OPLL), and to investigate whether SNPs of the Ser37Ala (T/G) and the Ser87Ser (A/G) in the BMP-2 gene are associated with genetic susceptibility to OPLL and its severity in Chinese subjects. The Ser87Ser (A/G) SNP has been implicated in bone mineral density (BMD) and increases the risk of OA in women. The Ser37Ala (T/G) SNP is associated with BMD and the rate of bone loss in osteoporosis and osteoporosis fractures. A total of 57 OPLL patients and 135 non-OPLL controls were studied. Radiographs of the cervical spine were analyzed to determine the presence and the severity of OPLL. The association of two SNPs with the occurrence and the extent of OPLL were statistically evaluated. There was a significant association between the Ser37Ala (T/G) polymorphism and the occurrence of OPLL in the cervical spine. However, no significant association was found between the Ser37Ala (T/G) polymorphism and the more number of ossified cervical vertebrae in OPLL patients. There was a significant association between the Ser87Ser (A/G) polymorphism and the more number of ossified cervical vertebrae in OPLL patients. However, there was no statistical difference between the Ser87Ser (A/G) SNP and the occurrence of OPLL in the cervical spine. In addition, the Ser87Ser (A/G) polymorphism in male patients and in female patients showed no statistical difference between cases and controls. The present results demonstrate that BMP-2 Gene is not only a factor associated with the occurrence of OPLL, but also a factor related to more extensive OPLL. The \”G\” allele in the Ser37Ala (T/G) polymorphism is associated with the occurrence of OPLL, but not more extensive OPLL in the cervical spine. The \”G\” allele in the Ser87Ser (A/G) polymorphism promotes the extent of OPLL, whereas the \”A\” allele in the Ser87Ser (A/G) polymorphism restricts ectopic ossification in the cervical spine at least in Chinese subjects.

Wang H, Liu D, Yang Z, Tian B, Li J, Meng X, Wang Z, Yang H, Lin X.

Beijing Tiantan Hospital, Capital Medical University (CMU), Beijing, 100050, China, haowang80@163.com.

Comparison of open versus percutaneous pedicle screw insertion in a sheep model.

Minimally invasive surgery has become more and more important for the treatment of traumatic spine fractures. Besides, some clinical studies, objective data regarding the possible lower damage to the surrounding tissue of the spine is still missing. Here we report a sheep model where we compared a percutaneous versus an open approach for dorsal instrumentation with pedicle screws to the spine. Twelve skeletally mature sheep underwent bilateral pedicle screw fixation at the L4-L6 level. Forty-eight pedicle screws were bilaterally inserted into the pedicles and connected with rods using either an open dorsal standard or a percutaneous approach. Operation time, blood flow, compartment pressure, radiation time, loss of blood, laboratory findings and EMG were evaluated to objectify possible advantages for the percutaneous operation technique. Loss of blood and the distribution of CK-MM as a marker for muscle damage were significantly lower in the percutaneous group. However, radiation time was significantly longer in the percutaneous group. Other parameters like compartment pressure, blood flow and also measurement of the EMG at different time points did not reveal significant differences. Based on the results we found in the present study, percutaneous screw insertion can bring moderate advantages but it should be noted that essential functional deficits to the muscle could not be detected.

Lehmann W, Ushmaev A, Ruecker A, Nuechtern J, Grossterlinden L, Begemann PG, Baeumer T, Rueger JM, Briem D.

Department of Trauma, Hand and Reconstructive Surgery, School of Medicine, Hamburg University, Martinistr. 52, 20246, Hamburg, Germany, wlehmann@uke.uni-hamburg.de.

Intramedullary hemangioblastomas: timing of surgery, microsurgical technique and follow-up in 23 patients.

Hemangioblastomas are highly vascularised tumors of the central nervous system and account for 1.5-2.5% of all spinal cord tumors. Because of the rarity of these tumors, surgical experience is often limited and, therefore, treatment and indications for timing of surgery are discussed controversial. The authors reviewed their data of 23 consecutive patients with respect to timing of surgery, microsurgical technique, and follow-up. Clinical records of 23 consecutive patients with intramedullary hemangioblastomas who underwent first surgery in our department between 1990 and 2005 were reviewed. In three cases the tumors were localised at the craniocervical junction; four patients had a single tumor in the cervical spine, six patients multiple tumors in the cervical and thoracic spine, eight patients in the thoracic spine only, one patient in the conus region, and one patient had multiple tumors located in the thoracic and lumbar spine. In eight patients, a von-Hippel-Lindau disease (VHL) was associated. The neurological follow-up was evaluated according to the classification of McCormick. Operation was recommended to every symptomatic patient as early as possible. In asymptomatic patients with a sporadic tumor surgery was discussed for diagnostic purposes at any time. In VHL patients, surgery was recommended if tumor growth was observed on MRI in the next practicable time. All tumors were diagnosed by magnetic resonance imaging and in all cases but one a DSA was performed. All patients were treated microsurgically through a posterior approach. The tumors in the spinal cord were removed microsurgically through a partial hemilaminectomy (n = 1), a hemilaminectomy (n = 15), or laminectomy (n = 4) and at the craniocervical junction (n = 3) through a suboccipital craniotomy. During follow-up after 6 months, 18 patients remained neurologically stable (17 in McCormick grade I and 1 in McCormick grade II) and 5 patients recovered to a better status (3 from grade III to II, 2 from grade II to I). There was one complication with a CSF fistula and one recurrence/incomplete removal. Following the above-mentioned principles of microsurgical removal of intramedullary hemangioblastomas, operation is possible with a low procedure-related morbidity and can be recommended especially in VHL patients with progressive symptoms or tumor growth during follow-up. Patients without VHL most frequently require hemangioblastoma resection for diagnostic purposes and/or because symptoms prompted an imaging work-up that lead to the discovery of the tumor.

Boström A, Hans FJ, Reinacher PC, Krings T, Bürgel U, Gilsbach JM, Reinges MH.

Department of Neurosurgery, University Hospital RWTH Aachen, Aachen, Germany, azize.bostroem@ukb.uni-bonn.de.

Relationship between the morphology of the atlanto-occipital joint and the radiographic results in patients with atlanto-axial subluxation due to rheumatoid arthritis.

The upper cervical spine is a common focus of destruction from rheumatoid arthritis (RA). Atlanto-axial subluxation (AAS) presents with marked frequency among patients with instability. However, there are occasional patients who show no motion between the occipital bone and atlas on a dynamic cervical radiograph in AAS patients. This study investigated the morphology of the atlanto-occipital joint (AOJ) in AAS patients due to RA using computed tomography, and examined the relationship between its morphology and other radiographic results. Twenty-six consecutive patients with AAS due to RA treated by surgery were reviewed. The subjects included 18 females and 8 males. The average patient age was 59.3 years. The mean duration of RA was 14.3 years. In all the patients, the AOJ was morphologically evaluated using sagittal reconstruction view on computed tomography before surgery. Moreover, the ADI value was investigated at the neutral and maximal flexion position, and atlanto-axial angle (AAA) at the neutral position in preoperative lateral cervical radiographs. The morphology of the AOJ on a CT sagittal reconstruction view was classified into three types as follows: a normal type which showed a maintenance of the joint space, a narrow type which showed a disappearance of the joint space and a fused type which showed the fusion of the AOJ. The pre-operative CT sagittal reconstruction image of the AOJ demonstrated a normal type bilaterally in six cases (Group A). In 15 cases (Group B), CT image demonstrated narrowing on at least one side of the AOJ. In five cases (Group C), CT images demonstrated fusion on at least one side of the AOJ. The average ADI value at the flexion position was 10.7 mm in Group A, 11.7 mm in Group B, and 12.6 mm in Group C. There was no significant difference among those groups. The average ADI value at the neutral position before surgery was 2.8 mm in Group A, 5.9 mm in Group B, and 10.4 mm in Group C. There was no significant difference between Group A and B (P > 0.105), and Groups B and C (P > 0.032), however, there was a significant difference between Groups A and C (P < 0.004). The average AAA value was 25.3 degrees in Group A, 19.3 degrees in Group B and 3.4 degrees in Group C. There was no significant difference between Groups A and B (P > 0.230), however, there was a significant difference between Groups A and C (P < 0.002), and Groups B and C (P < 0.007). This study showed that fusion or ankylosis of the AOJ induced an enlargement of the ADI and anterior inclination of the atlas in the neutral position, despite the fact that normal findings of AOJ showed a slight displacement of the atlas to axis in RA patients showing AAS involvement. This morphology may progress to SAS and VS due to AOJ after atlanto-axial arthrodesis.

Iizuka H, Sorimachi Y, Ara T, Nishinome M, Nakajima T, Iizuka Y, Takagishi K.

Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511, Japan, ihaku@showa.gunma-u.ac.jp.

Quality of sleep in patients with chronic low back pain: a case-control study.

Animal experiments and studies in humans clearly show that the relation between pain (acute and chronic) and sleep quality is two-way: sleep disorders can increase pain, which in turn may cause sleep disorders. Sleep disorders and chronic low back pain are frequent health problems and it is unsurprising that the two can co-exist. This study was conducted to evaluate if sleep disorders and chronic pain associated are more frequently than one would expect. The objective of the study was to compare sleep quality in a population of patients with chronic low back pain and a control population. Sleep quality was assessed in 101 patients with chronic low back pain (CLBP) and in 97 sex- and age-matched healthy control subjects using the Pittsburgh Sleep Quality Index [PSQI; score from 0 (no disorder) to 21]. The French version of the Dallas Pain Questionnaire (DPQ) was used to assess the impact of low back pain on patients\’ quality of life. This impact was taken as nil in the healthy controls. The patients with CLBP and the controls were comparable in age, sex, and height, but mean bodyweight was higher in the CLBP group (70.3 +/- 14.5 vs. 61.8 +/- 11.4 kg; P < 0.05). The patients with CLBP were also more frequently on sick leave than the controls (32.3%; n = 31 vs. 0.0% n = 0; P < 0.001). Coffee, tea, and cola intakes were comparable in the two groups. Patients with CLBP had statistically higher scores in all items of the PSQI than the healthy controls. The mean PSQI was 4.7 +/- 3.2 for the healthy controls and 10.9 +/- 7.9 for the patients with CLBP (P < 0.0001). Sleep disorders were greater when the impact of CLBP on daily life (the four aspects of the DPQ) was greater [P < 0.0001]). The sleep of the patients with CLBP was significantly altered compared with that of the healthy controls, in proportion to the impact of low back pain on daily life. Our findings do not indicate whether sleep disorders are a cause or a consequence of CLBP.

Marty M, Rozenberg S, Duplan B, Thomas P, Duquesnoy B, Allaert F; The Section Rachis de la Société Française de Rhumatologie.

Service de rhumatologie, Hôpital H Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94 000, Creteil, France, marc.marty@free.fr.

High glucose promotes collagen synthesis by cultured cells from rat cervical posterior longitudinal ligament via transforming growth factor-beta1.

Non-insulin-dependent diabetes is known as a risk factor of ossification of posterior longitudinal ligament, but the mechanism has not been well understood. We hypothesized that hyperglycemia, as a typical characteristic of diabetes, is closely associated with ligament hypertrophy in ossification of posterior longitudinal ligament. In this in vitro study, we investigated the effect of high glucose on collagen synthesis and transforming growth factor-beta1 (TGF-beta1) production using cells isolated from rat cervical posterior longitudinal ligament. The cells were subjected to high D: -glucose concentration (25 mM) media for 4 days. Notable increases were observed in gene expression and protein synthesis of collagen types I, III in the cells. The increase was inhibited in the presence of anti-TGF-beta1 antibodies. Production of TGF-beta1 by the cells was also increased significantly by high glucose concentration. Exogenous application of TGF-beta1 was confirmed to increase collagen synthesis of the cells. These data suggested that high glucose could promote collagen synthesis in the posterior longitudinal ligament mainly via endogenous TGF-beta1, resulting in hypertrophy of the ligament.

Li H, Liu D, Zhao CQ, Jiang LS, Dai LY.

Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, 200092, Shanghai, China.