Cervical Disc Replacement for Spondylotic Myeloradiculopathy

Background

Cervical disc replacement is a newer concept and rapidly developing surgical treatment. A prospective study was conducted to determine, if accurately implanted Bryan''s cervical disc prostheses can provide relief from objective neurological symptoms and signs, stability and normal range of motion in cases of cervical disc prolapse with myeloradiculopathy.

Material and Method

Twenty patients underwent Bryan cervical disc replacement from Jan 2002 to Dec 2003. Young patients between age groups 21 to 50 years with degenerative cervical disc prolapse at C3-C7 with myeloradiculopathy were included in this study. Patients with significant facet joint arthropathy, unstable spine, trauma, tumour, osteoporosis and active infection were excluded from this study. Nurick''s grading was used for quantifying the neurological deficit. Patients were operated by anterior cervical approach using a specially designed Bryan''s cervical discectomy system. Neurological and radiological outcome was assessed post operatively and at 2,6,12 and 24 months follow up. Outcome analysis was carried out using modified Odom''s criteria. The radiographic results were assessed by taking antero posterior (AP) and lateral radiographs of cervical spine to find range of motion and device position.

Results

The patients were in the age group of 31 to 50 years. There were 14 (70%) male and 6 (30%) female in this study. Neck pain and brachialgia were the presenting symptoms in all cases, 12 (60%) had radiculopathy and 8 (40%) had myelopathy. Single level disc prolapse was present as per Magnetic Resonance Imaging (MRI) in four (20%) at C4-C5, 12 (60%) at C5-C6 and 4 (20%) at C6-C7. Bryan''s disc size 15 was used in 8 (40%) and size 17 was used in 12(60%) patients. During post-operative, 02, 06, 12, and 24 months follow up, the clinical outcome was excellent in 16 (80%) and good in 4 (20%) as per modified Odom''s criteria. There was demonstrated improvement in flexion, extension and rotation clinically and radiologically during follow up. There was no migration or displacement of device.

Conclusion

Cervical disc replacement for cervical disc prolapse with myeloradiculopathy represents an exciting new technology. Patients treated with the Bryan cervical disc prosthesis for single level cervical disc prolapse showed good to excellent improvement in neurological deficit. Clinically and radiologically maintenance of motion was found during follow up. More patients with longer follow up and post operative MRI to find out the protection to adjacent discs from abnormal stress will be required before this prosthesis is accepted as a treatment option.Key Words: Spondylotic myeloradiculopathy, Cervical disc replacement     

Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.     

A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12)     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Human immunodeficiency virus seroprevalence among blood product recipients in San Francisco before transfusion

To determine the incidence of transfusion-associated human immunodeficiency virus (HIV) infection after routine screening of donated blood, a pilot study estimated the pretransfusion prevalence of HIV infection among blood product recipients in San Francisco. Among the 911 nonduplicate pretransfusion specimens from recipients without a clinical history of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the overall prevalence of antibody to HIV was 2.9 percent (5.2% among males and 0.6% among females; p = 0.00002). If recipients in specifically defined or possible high-risk groups (n = 348) were excluded, a seropositivity rate of 1.8 percent (10/563) was detected, with all the positives occurring in men (10/242, 4.1%) and none in women (0/321, 0%). This demonstrated prevalence of HIV infection among blood product recipients in San Francisco before transfusion was substantially higher than the known 0.02 to 0.04 percent prevalence in the donor population. Therefore, the population of women without known risk for AIDS is the best in which to assess the risk of HIV infection in patients who are currently receiving seronegative blood transfusions.     

Fluorescent in vivo tracking of hematopoietic cells. Part I. Technical considerations

We report a new technology for in vivo tracking of hematopoietic cells, using fluorescent lipophilic probes. Because the probe is irreversibly bound in the lipids of the cell membrane; substantial numbers of dye molecules can be incorporated per cell and thus substantial signal to noise can be achieved. Although this technology can be used for all hematopoietic cells, these first findings are reported on red blood cells (RBCs) owing to the importance of the membrane to RBC function and integrity. We demonstrated that labeling 10% of the RBCs of a rabbit and reinjecting them into the animal makes possible the tracking of these cells at various times after injection. Furthermore, the labeling appears not to affect in vivo cell lifetime or cellular volume changes in response to hypotonic shock. The single cell fluorescence intensity of the labeled RBCs remains relatively constant for 60 days, and an immune response appears not to be generated against labeled cells. That labeled RBCs have lifetime kinetics in vivo, as shown in other studies, indicates that the membranes are functioning normally and are unaltered by the labeling technology. The technology we present is also applicable to white blood cells, bone marrow, and platelets.