George Ehni, Richard H. Moiel and T. Guy Bragg
Rob D. Dickerman, Ashley S. Reynolds, Jack Zigler and Richard Guyer
Mark N. Hadley
Michael D. Dan, Christopher M. Schlachta, John Guy, Richard G. McKenzie, Delbert R. Dorscheid, Victor A. Sandor, Jean-Guy Villemure and Gerald B. Price
✓ The current management of malignant gliomas is unsatisfactory compared to that of other solid tumors; the expected median survival period is less than 1 year with the patient undergoing conventional surgery, radiotherapy, and chemotherapy treatment. Immunological reagents could be a useful adjunct. Human monoclonal antibodies derived from patients with astrocytic tumors might recognize subtle antigenic specificities that would differ from those recognized by xenogeneic (murine) systems. Five hybridomas, designated as BT27/1A2, BT27/2A3, BT32/A6, BT34/A5, and BT54/B8, were produced from the fusion of peripheral blood lymphocytes of four patients with astrocytic tumors to the human myeloma-like cell line TM-H2-SP2. This cell line has a 46, XX karotype and is negative for hypoxanthine guanine phosphoribosyltransferase. All five human monoclonal antibodies produced 2.4 to 44 µg/ml of immunoglobulin M, had a similar but not identical pattern of reactivity against a panel of human tumor cell lines, and failed to react with normal human astrocytes. Labeling of four neuroectodermal tumor explant cultures by BT27/2A3 was demonstrated by flow cytometry. Karyotyping of three of the five hybridomas demonstrated that two were pseudodiploid (2–3n) and one hypodiploid (< 2n). The monoclonality of the hybridomas was evaluated by Southern blot analysis of JH gene rearrangements, revealing two types of rearrangements for each hybridoma, both consistent with monoclonality. Preliminary antigen characterization indicated that at least four of the five human monoclonal antibodies were directed to cell-surface glycolipids.
Guy L. Clifton, Claudia S. Robertson, Robert G. Grossman, Susan Hodge, Richard Foltz and Cutberto Garza
✓ Caloric expenditure and nitrogen balance were measured in 14 steroid-treated comatose head-injured patients acutely and up to 28 days after injury. During this period patients were fed with a continuous enteral infusion of a formula containing 2 Kcal/cc and 10 gm nitrogen/liter. Indirect calorimetry was carried out for 102 patient-days. The mean resting metabolic expenditure (RME) for nonsedated nonparalyzed patients was 138% ± 37% of that expected for an uninjured resting person of equivalent age, sex, and body surface area. Nitrogen excretion was measured for 135 patient-days. The mean excretion was 20.2 ± 6.4 gm/day. The mean protein caloric contribution was 23.9% ± 6.7% and was greater than 25% for six patients, compared to normal values of 10% to 15%. Despite hyperalimentation, positive nitrogen balance for any 3-day period was achieved in only seven patients, and required replacement of 161% to 240% of RME with enterally administered formula. Head-injured patients had a metabolic response similar to that reported for patients with burns of 20% to 40% of the body surface.
Neurological complications of lumbar artificial disc replacement and comparison of clinical results with those related to lumbar arthrodesis in the literature: results of a multicenter, prospective, randomized investigational device exemption study of Charité intervertebral disc
Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004
Fred H. Geisler, Scott L. Blumenthal, Richard D. Guyer, Paul C. McAfee, John J. Regan, J. Patrick Johnson and Bradford Mullin
Object. Arthrodesis is the gold standard for surgical treatment of lumbar degenerative disc disease (DDD). Solid fusion, however, can cause stress and increased motion in the segments adjacent to the fused level. This may initiate and/or accelerate the adjacent-segment disease process. Artificial discs are designed to restore and maintain normal motion of the lumbar intervertebral segment. Restoring and maintaining normal motion of the segment reduces stresses and loads on adjacent level segments. A US Food and Drug Administration Investigational Device Exemptions multicentered study of the Charité artificial disc was completed. The control group consisted of individuals who underwent anterior lumbar interbody fusion involving BAK cages and iliac crest bone graft. This is the first report of Class I data in which a lumbar artificial disc is compared with lumbar fusion.
Methods. Of 304 individuals enrolled in the study, 205 were randomized to the Charité disc-treated group and 99 to the BAK fusion—treated (control) group. Neurological status was equivalent between the two groups at 6, 12, and 24 months postoperatively. The number of patients with major, minor, or other neurological complications was equivalent. There was a greater incidence of both major and minor complications in the BAK fusion group at 0 to 42 days postoperatively. Compared with data reported in the lumbar fusion literature, the Charité disc—treated patients had equivalent or better mean changes in visual analog scale and Oswestry Disability Index scores.
Conclusions. The Charité artificial disc is safe and effective for the treatment of single-level lumbar DDD, resulting in no higher incidence of neurological complications compared with BAK-assisted fusion and leading to equivalent or better outcomes compared with those obtained in the control group and those reported in the lumbar fusion literature.
Ronald L. Hayes, Bruce G. Lyeth, Larry W. Jenkins, Richard Zimmerman, Tracy K. McIntosh, Guy L. Clifton and Harold F. Young
✓ Naloxone (0.1, 1.0, or 20.0 mg/kg), morphine (1.0 or 10.0 mg/kg), or saline was administered systemically intraperitoneally to rats 15 minutes prior to moderate fluid-percussion brain injury. The effects of the drugs were measured on systemic physiological, neurological, and body-weight responses to injury. The animals were trained prior to injury and were assessed for 10 days after injury on body-weight responses and neurological endpoints. Low doses of naloxone (0.1 or 1.0 mg/kg) significantly exacerbated neurological deficits associated with injury. Morphine (10.0 mg/kg) significantly reduced neurological deficits associated with injury. The drugs had no effect on neurological measures or body weight in sham-injured animals. Drug treatments did not significantly alter systemic physiological responses to injury. Data from these experiments suggest the involvement of endogenous opioids in at least some components of neurological deficits following traumatic brain injury and suggest the possibility that at least some classes of endogenous opioids may protect against long-term neurological deficits produced by fluid-percussion injury to the rat.
Paul C. McCormick
Richard D. Guyer, Fred H. Geisler, Scott L. Blumenthal, Paul C. McAfee and Bradford B. Mullin
Lumbar arthroplasty is approved in the US for the treatment of degenerative disc disease at 1 level in skeletally mature patients. However, a bias toward older patients (> 45 years of age) who are otherwise indicated for the procedure may exist. In this study, the clinical outcomes of patients from the Charité Investigational Device Exemption (IDE) study were analyzed on the basis of patient age.
There were 276 patients enrolled in the IDE study of the Charité Artificial Disc who underwent 1-level arthroplasty at either L4–5 or L5–S1, including 71 nonrandomized and 205 randomized individuals. Patient data were analyzed based on age (18–45 years [217 patients, Group 1] compared with 46–60 years [59 patients, Group 2]). Statistical analyses were performed based on 2-year postoperative improvements in Oswestry Disability Index (ODI), 36-item Short Form Health Survey (SF-36), and visual analog scale (VAS) scores (clinical outcome), as well as range of motion (radiographic outcome), and adverse events.
There was no significant difference between the groups with respect to level implanted, operative time, blood loss, changes in ODI and VAS scores or any of the 8 component scores of the SF-36, compared with baseline, at all time points throughout the 24-month follow-up period (p > 0.10). Patient satisfaction was equivalent at 24 months, with 87% satisfaction in Group 1 and 85% satisfaction in Group 2 (no statistical difference). In addition, no significant differences were identified with respect to adverse events including approach related, neurological, technique related, or reoperation.
Although patients > 45 years of age may have comorbidities or contraindications for arthroplasty for a number of reasons, particularly osteopenia, this analysis demonstrates that patients who are indicated for 1-level arthroplasty experience similar clinical outcome, satisfaction, or adverse events compared with their younger counterparts.
Toru Fukuhara, Guy M. McKhann II, Paul Santiago, Joseph M. Eskridge, John D. Loeser and H. Richard Winn
✓ The authors describe a patient with right-sided central pain resulting from a left parietal arteriovenous malformation (AVM). The AVM was treated with staged embolization and stereotactic radiosurgery, and its obliteration was documented on follow-up angiographic studies. Surprisingly, the patient noted complete resolution of her pain syndrome after embolization, which is an extremely rare result. Central pain and its proposed mechanisms are discussed.