Outcomes following surgical intervention for impending and gross instability caused by multiple myeloma in the spinal column.

OBJECT: Multiple myeloma is the most common primary tumor of the spine and is the most common primary malignant tumor of bone. Although spinal myeloma is classically a radiosensitive lesion, clinical or radiographic signs of instability merit surgical intervention. The authors present the epidemiology, surgical indications, and outcome data of a series of consecutive cases involving 31 surgically treated patients with diagnoses of multiple myeloma and plasmacytoma of the spine (the largest such series reported to date). METHODS: Surgical instability was the criterion for operative intervention in this patient cohort. The Spinal Instability Neoplastic Score (SINS) was used to make this assessment of instability. The cases were analyzed using location of the lesion, spinal levels involved, Frankel score, adjuvant therapy, functional outcome, and patient survival. RESULTS: All patients undergoing surgical intervention were determined to have indeterminate or gross spinal column instability according to SINS criteria. The median survival was 78.9 months. No significant difference in survival was seen for patients with higher SINS scores or for older patients (> 55 years). There was a statistically significant difference in survival benefit observed for patients receiving chemotherapy and radiation versus radiation alone as an adjuvant to surgery (p = 0.02). CONCLUSIONS: In this 10-year analysis, the authors report outcomes of surgical intervention for patients with indeterminate or gross spinal instability due to multiple myeloma and plasmacytoma of the spine with improved neurological function following surgery and low rates of instrumentation failure.

Biomechanical evaluation of the pedicle screw insertion depth effect on screw stability under cyclic loading and subsequent pullout.

STUDY DESIGN: A biomechanical ex vivo study of the human lumbar spine. OBJECTIVE: To evaluate the effects of transpedicular screw insertion depth on overall screw stability and pullout strength following cyclic loading in the osteoporotic lumbar spine. SUMMARY OF BACKGROUND DATA: Although much is known about the clinical outcomes of spinal fusion, questions remain in our understanding of the biomechanical strength of lumbar pedicle screw fixation as it relates to screw sizing and placement. Biomechanical analyses examining ideal pedicle screw depth with current pedicle screw technology are limited. In the osteoporotic spine, optimized pedicle screw insertion depth may improve construct strength, decreasing the risk of loosening or pullout. METHODS: A total of 100 pedicles from 10 osteoporotic lumbar spines were randomly instrumented with pedicle screws in mid-body, pericortical, and bicortical depths. Instrumented specimens underwent cyclic loading (5000 cycles of ±2 N m pure flexion moment) and subsequent pullout. Screw loosening, failure loads, and energy absorption were calculated. RESULTS: Cyclic loading significantly (P<0.001) reduced screw-bone angular stiffness between prefatigue and postfatigue conditions by 25.6%±17.9% (mid-body), 20.8%±14.4% (pericortical), and 14.0%±13.0% (bicortical). Increased insertion depth resulted in lower levels of reduction in angular stiffness, which was only significant between mid-body and bicortical screws (P=0.009). Pullout force and energy of 583±306 N and 1.75±1.98 N m (mid-body), 713±321 N and 2.40±1.79 N m (pericortical), and 797±285 N and 2.97±2.33 N m (bicortical) were observed, respectively. Increased insertion depth resulted in higher magnitudes of both pullout force and energy, which was significant only for pullout force between mid-body and bicortical screws (P=0.005). CONCLUSION: Although increased screw depth led to increased fixation and decreased loosening, additional purchase of the stiff anterior cortex is essential to reach superior screw-bone construct stability and stiffness.

Malignant peripheral nerve sheath tumor of the vestibulocochlear nerve and brainstem: multimodality treatment with survival of 27 months. A case report and review of the literature.

BACKGROUND AND IMPORTANCE: Malignant peripheral nerve sheath tumors are the most common malignant mesenchymal tumors of soft tissues, but they are very rare when found to arise from a cranial nerve and when not in association with neurofibromatosis. These tumors are highly malignant and carry a poor prognosis with survival usually less than 6 months. CLINICAL PRESENTATION: The authors report the case of a 23-year-old female with no history of phakomatoses, previous irradiation, or known genetic disorders, who presented with a malignant peripheral nerve sheath tumor of the vestibulocochlear nerve and brainstem. Multiple staged skull base approaches were carried out with maximal possible resection. Adjunctive therapies including standard radiation therapy, intensity-modulated radiation therapy, and stereotactic gamma knife radiosurgery were used with an ultimate patient survival of 27 months. CONCLUSION: To our knowledge, this is the first report describing a patient with a malignant peripheral nerve sheath tumor of the vestibulocochlear nerve and brainstem treated with staged surgical approaches in conjunction with multiple forms of radiotherapy and having a significant survival of more than 2 years.

Simultaneous choroid plexus carcinoma and pilocytic astrocytoma in a pediatric patient.

Simultaneous primary brain tumors in pediatric patients without prior chemotherapy or radiotherapy, phacomatosis, or known familial history are a rare occurrence. The authors report the case of a 4-year-old boy with simultaneous choroid plexus carcinoma and pilocytic astrocytoma with features of oligodendroglioma. Magnetic resonance imaging studies revealed diffuse heterogeneously enhancing left intraventricular and posterior fossa tumors initially believed most consistent with multicentric choroid plexus carcinomas. A multiple staged resection was carried out for each tumor and gross-total resection was achieved. Upon gross inspection intraoperatively as well as postoperative histological analysis, 2 distinct simultaneous tumors were identified: choroid plexus carcinoma and pilocytic astrocytoma. To the authors' knowledge this is the first case report published identifying 2 distinct tumor types with similar radiological appearances in a pediatric patient with no prior history of radiotherapy, chemotherapy, or phacomatosis.

Effect of food deprivation and hormones of glucose homeostasis on the acetyl CoA carboxylase activity in mouse brain: a potential role of acc in the regulation of energy balance.

We studied the regulation of brain acetyl CoA carboxylase (ACC) activity during food deprivation and under the influence of hormones of glucose homeostasis: glucagon and insulin. Mice were deprived of food and water for time periods of 1, 3, 6, 9, 12 and 24 hours and were then allowed to re-feed for 5, 30 and 60 minutes. Mice that were deprived for up to 6 h, and then re-fed for 60 min, consumed the same amount of food compared to the ad libitum (control) animals. However, after 9 h of deprivation, mice consumed only 50% of food present even after 1 h of re-feeding, compared to the controls. The ACC activity was measured in the whole mouse brain of controls and after 1, 3, 6, 9, 12, and 24 h of food deprivation. Brain extracts assayed from control mice expressed an ACC activity of 0.988 +/- 0.158 fmol/min/mg tissue without citrate and 0.941 +/- 0.175 fmol/min/mg tissue with citrate. After 1 h of food deprivation, the total ACC activity without citrate decreased to 0.575 +/- 0.087 fmol/min/mg and in the presence of citrate, 0.703 +/- 0.036 fmol/min/mg activity was measured. The citrate-dependent ACC activity decreased over time, with only 0.478 +/- 0.117 fmol/min/mg of activity remaining after 24 h. Intraperitoneal (i.p.) injections of insulin, glucagon and phosphate buffered saline (PBS) were performed and whole brain ACC activity measured. After hormone administration, there were no significant differences in ACC activity in the presence of citrate. However, in the absence of citrate, there was a significant 20% decrease in ACC activity with glucagon (1.36 +/- 0.09 fmol/min/mg) and a 33% increase with insulin (2.49 +/- 0.11 fmol/min/mg) injections compared to PBS controls (1.67 +/- 0.08 fmol/min/mg). Neuropeptide Y (NPY) levels of corresponding brain extracts were measured by ELISA (OD) using anti-NPY antibody and showed an 18% decrease upon insulin injection (0.093 +/- 0.019) and a 50% increase upon glucagon injection (0.226 +/- 0.084) as compared to controls injected with PBS (0.114 +/- 0.040). Thus, we postulate that the changes in ACC levels under metabolic conditions would result in a fluctuation of malonyl CoA levels, and subsequent modulation of NPY levels and downstream signaling.

Isolation, partial purification, and characterization of a novel petromyzonol sulfotransferase from Petromyzon marinus (lamprey) larval liver.

We have isolated, partially purified, and characterized the 5 alpha-petromyzonol (5 alpha-PZ), (5 alpha-cholan- 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-) sulfotransferase (PZ-SULT) from larval lamprey liver. Crude liver extracts exhibited a PZ-SULT activity of 0.9120 pmol/min/mg in juvenile and 12.62 pmol/min/mg in larvae. Using crude larval liver extracts and various 5 beta-cholan substrates and allocholic acid there was negligible activity, however, with 5 alpha-PZ and 3-keto-5 alpha-PZ the SULT activity was 231.5 pmol/min/mg and 180.8 pmol/min/mg respectively. This established that the sulfotransferase of lamprey larval liver extracts prefers (5 alpha) substrates and it is selective for hydroxyl at C-24. PZ-SULT was purified through various chromatography procedures. Partially purified PZ-SULT exhibited a pH optimum of 8.0, a temperature optimum of 22 degrees C, and activity was linear for 1h. PZ-SULT exhibited a K(m) of 2.5 microM for PAPS and a K(m) of 8 microM for PZ. The affinity purified peak PZ-SULT exhibited a specific activity of 2,038 pmol/min/mg. The peak protein upon SDS-PAGE, correlated to an Mw 47 kDa. Photoaffinity labeling with PAP(35)S, specifically crosslinked the 47 kDa protein, further confirming the identity of PZ-SULT. Partial amino acid sequencing of the putative 47 kDa PZ-SULT protein yielded a peptide sequence (M)SISQAVDAAFXEI, which possessed an overall (approximately 35-40%) homology with mammalian SULT2B1a.