Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model.

Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 µg + 0 µg, B: 0.1 µg + 0.1 µg, C: 1 µg + 1 µg, and D: 10 µg + 10 µg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 µgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.

Gene knockdown of the N-methyl-D-aspartate receptor NR1 subunit with subcutaneous small interfering RNA reduces inflammation-induced nociception in rats.

BACKGROUND: Spinal N-methyl-D-aspartate receptors have been demonstrated to play an important role in the facilitation and maintenance of nociception. To avoid adverse effects of blocking N-methyl-D-aspartate receptors in the central nervous system, blocking N-methyl-D-aspartate receptor in peripheral nervous system is an ideal alternative. Transfection of small interfering RNAs (siRNAs) into cells has been revealed to provide potent silencing of specific genes. In this study, the authors examined the effect of subcutaneous injection of siRNA targeting the NR1 subunit of the N-methyl-D-aspartate receptor on silencing NR1 gene expression and subsequently abolishing inflammatory nociception in rats. METHODS: Male Sprague-Dawley rats received intradermal injection of NR1 siRNA and underwent injection of formalin or complete Freund's adjuvant. The flinch response and mechanical hypersensitivity by von Frey filaments were assessed. Then the messenger RNA and protein of NR1 in skin and dorsal root ganglion were analyzed. RESULTS: The results revealed that subcutaneous injection of 1 nmol NR1 siRNA effectively diminished the nociception induced by formalin and complete Freund's adjuvant stimuli and attenuated the level of NR1 messenger RNA and protein in skin and ipsilateral dorsal root ganglion. The antinociception effect and the inhibition of NR1 expression persisted for about 7 days after administration of NR1 siRNA. CONCLUSIONS: The data of this study suggest that NR1 siRNA has potential therapeutic value in the treatment of inflammatory pain induced or maintained by peripheral nociceptor activity and support the potential application of this method to the study of nociceptive processes and target the validation of pain-associated genes.

Therapeutic potential of RNA interference in pain medicine.

In recent years RNA interference (RNAi) has rapidly become the most widely used tool for gene knockdown due to its high specificity and potency. RNAi is an evolutionarily conserved mechanism for silencing gene expression by targeted degradation of mRNA. In the past decade, hundreds of molecular targets have been identified for their roles in pain modulation. But most molecular targets are not readily druggable with small molecules. RNAi represents a therapeutic approach applicable to these non-druggable targets. There is a rapid increase in the number of studies that use small interfering RNAs (siRNAs) to validate new targets for pain regulation. In this review, we will discuss these pain-related RNAi studies (Table 1). We will also compare the advantages and disadvantages of RNAi with antisense knockdown (Table 2), because antisense oligodeoxynucleotides have been extensively used for target validation in pain research. Although in vivo delivery of siRNA remains to be a challenge, RNAi has a great potential to become a major therapeutic tool for pain management.

Sevoflurane with or without antiemetic prophylaxis of dexamethasone in spontaneously breathing patients undergoing outpatient anorectal surgery.

STUDY OBJECTIVE: To evaluate the prophylactic use of dexamethasone with sevoflurane in outpatient anorectal surgery. DESIGN: Randomized, controlled study. SETTING: Operating room and Postanesthesia Care Unit of a general hospital. PATIENTS: 60 adult, ASA physical status I and II outpatients undergoing anorectal surgery. INTERVENTIONS: Patients were randomized to receive either dexamethasone 5 mg intravenously (IV; Group D; n = 30) or an equal volume of saline (Group S; n = 30) before anesthesia induction. Anesthesia was induced with propofol 2.5 mg.kg(-1), fentanyl two microg.kg(-1), and 2% lidocaine one mg.kg(-1) followed by placement of a Laryngeal Mask Airway. MEASUREMENTS: Frequency of postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, and patient satisfaction were recorded. MAIN RESULTS: Frequency of PONV and VAS pain scores were significantly lower in Group D than Group S (P < 0.05). The time required for "home readiness" was significantly shorter in Group D than Group S (P < 0.05). CONCLUSIONS: The prophylactic administration of 5 mg dexamethasone IV can reduce the frequency of PONV, lower VAS pain scores, facilitate recovery to home readiness, and improve satisfaction in outpatients undergoing anorectal surgery.

Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis.

The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.

Comparing the use of the Taiwanese Depression Questionnaire and Beck Depression Inventory for screening depression in patients with chronic pain.

BACKGROUND: Studies have shown that the validity of self-reported depression questionnaires may be influenced by somatic symptoms such as chronic pain. The purpose of this study was to compare the validity of two self-reported questionnaires, the Taiwanese Depression Questionnaire (TDQ) and the Beck Depression Inventory (BDI), for screening depression in patients with chronic pain. METHODS: One hundred patients with chronic pain were enrolled and assessed using the TDQ, BDI, McGill Pain Questionnaire, and Structured Clinical Interview for DSM-III-R. Seventy-three of them were diagnosed with depressive disorders. Conventional validity indices of the TDQ and BDI were examined and compared. RESULTS: Both the TDQ and BDI had satisfactory sensitivity, specificity, positive predictive value, and negative predictive value. Our results showed a trend that the validity of the TDQ was better than that of the BDI, and the validity of the cognitive/affective components of the TDQ was significantly better than that of the BDI. CONCLUSION: Our results suggest that the TDQ is superior to the BDI in detecting depression in patients with chronic pain in Taiwan.

A novel vector system for gene transfer into the cornea using a partially dried plasmid expressing 18 basic fibroblast growth factor-synthetic amphiphile INTeraction-18 (SAINT-18) complex.

PURPOSE: We describe a novel vector system of nonviral gene transfer into the cornea using a partially dried form of a plasmid expressing 18-kDa basic fibroblast growth factor (p-bFGF)-synthetic amphiphile INTeraction-18 (SAINT-18) complex. METHODS: Corneal neovascularization (NV) was evaluated in 48 eyes of Sprague-Dawley rats after implantation of SAINT-18 containing 2 micro g of plasmid-expressing green fluorescent protein (p-GFP; control group), 0.2 micro g, 2 micro g, or 20 micro g of p-bFGF from day 0 to day 60. bFGF protein expression was analyzed by Western blotting and immunohistochemistry. RESULTS: The p-bFGF-SAINT-18 complex induced dose-dependent corneal neovascularization, which reached a maximum on days 15-21 in the 20-micro g p-bFGF group, days 12-18 in the 2-micro g p-bFGF group, and on days 9-15 in the 0.2-micro g p-bFGF group, and then regressed progressively. No NV was observed in the p-GFP group. CONCLUSIONS: This noninflammatory corneal transfection model using partially dried p-bFGF-SAINT-18 complex allows precise localization of tranfection reagents for producing corneal neovascularization.

Preincisional subcutaneous infiltration of ketamine suppresses postoperative pain after circumcision surgery.

OBJECTIVE: N-methyl-D-aspartate and other glutamate receptors have been shown to present on the peripheral axons of primary afferents, and peripheral injection of N-methyl-D-aspartate-receptor antagonists can suppress hyperalgesia and allodynia. Thus, this study examined postoperative analgesic and adverse effects of local ketamine administered postoperatively. METHODS: Ketamine (0.3%, 3 mL) or saline was subcutaneously infiltrated before incision in a double-blind manner using a sample population of 40 patients undergoing circumcision surgery, equally and randomly assigned to 2 groups based on the treatment. The saline-infiltrated patients also received 9-mg intramuscular ketamine into the upper arm to control for any related systemic analgesic effects. The patients were followed up for 24 hours to determine postoperative analgesia and identify adverse effects. RESULTS: In the ketamine-infiltrated patients, the time interval until first analgesic demand (166 vs. 80 min) was longer and the incidence of pain-free status (pain score=0) during movement (45% vs. 10%) and erection (40% vs. 0%) was significantly higher than for the saline-treated analogs (P<0.05). The dose of ketorolac use and pain score during erection were significant lower in group ketamine patients. No significant differences were noted with respect to the incidence of adverse effects comparing the 2 groups. DISCUSSION: We conclude that preincisional subcutaneous ketamine infiltration can suppress postoperative pain after the circumcision surgery.

Heme oxygenase 1, nuclear factor E2-related factor 2, and nuclear factor kappaB are involved in hemin inhibition of type 2 cationic amino acid transporter expression and L-Arginine transport in stimulated macrophages.

BACKGROUND: L-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and L-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappaB (NF-kappaB) were also investigated. METHODS: Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 microm), lipopolysaccharide plus hemin (5, 50, or 500 microm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 microm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed. RESULTS: Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-kappaB activation, CAT-2 expression, and L-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-kappaB activation, CAT-2 expression, and L-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin. CONCLUSIONS: HO-1 induction significantly inhibited CAT-2 expression and L-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-kappaB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and L-arginine transport.

Combined subdural and epidural block in a case of epidural catheterization for postoperative analgesia.

We report a case of unusual block caused by postoperative epidural analgesia for laparotomy in a gynecologic patient in consequence of inadvertent epidural catheterization. The clinical manifestation included agitation, spotty distribution of analgesia, wide spread of sensory block and loss of motor power. The radiological findings suggested a multicompartmental block with the anchorage of the catheter tip stretching over the epidural and subdural spaces. The default of catheter position was not detected during routine test dose procedure.

Gene transfer of pro-opiomelanocortin prohormone suppressed the growth and metastasis of melanoma: involvement of alpha-melanocyte-stimulating hormone-mediated inhibition of the nuclear factor kappaB/cyclooxygenase-2 pathway.

Pro-opiomelanocortin (POMC) is a prohormone of various neuropeptides, including corticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), and beta-endorphin (beta-EP). POMC neuropeptides are potent inflammation inhibitors and immunosuppressants and may exert opposite influences during tumorigenesis. However, the role of POMC expression in carcinogenesis remains elusive. We evaluated the antineoplastic potential of POMC gene delivery in a syngenic B16-F10 melanoma model. Adenovirus-mediated POMC gene delivery in B16-F10 cells increased the release of POMC neuropeptides in cultured media, which differentially regulated the secretion of pro- and anti-inflammatory cytokines in lymphocytes. POMC gene transfer significantly reduced the anchorage-independent growth of melanoma cells. Moreover, pre- or post-treatment with POMC gene delivery effectively retarded the melanoma growth in mice. Intravenous injection of POMC-transduced B16-F10 cells resulted in reduced foci formation in lung by 60 to 70% of control. The reduced metastasis of POMC-transduced B16-F10 cells could be attributed to their attenuated migratory and adhesive capabilities. POMC gene delivery reduced the cyclooxygenase-2 (COX-2) expression and prostaglandin (PG) E(2) synthesis in melanoma cells and tumor tissues. In addition, application of NS-398, a selective COX-2 inhibitor, mimicked the antineoplastic functions of POMC gene transfer in melanoma. The POMC-mediated COX-2 down-regulation was correlated with its inhibition of nuclear factor kappaB (NFkappaB) activities. Exogenous supply of alpha-MSH inhibited NFkappaB activities, whereas application of the alpha-MSH antagonist growth hormone-releasing peptide-6 (GHRP-6) abolished the POMC-induced inhibition of NFkappaB activities and melanoma growth in mice. In summary, POMC gene delivery suppresses melanoma via alpha-MSH-induced inhibition of NFkappaB/COX-2 pathway, thereby constituting a novel therapy for melanoma.

The effect of acute smoking on spinal fusion: an experimental study among rabbits.

BACKGROUND: The establishment of an environment to force animals to inspire cigarette smoke is mandatory to study the true effects of smoking. This model has been used to study long-bone healing but has not yet been used to study spinal fusion. METHODS: Forty male rabbits were divided into four equal groups. All the animals underwent bilateral intertransverse-process fusion at L5-L6 using the 1995 fusion model of Boden et al. The first (C8-week) group did not undergo cigarette smoke inhalation and individual rabbits were killed at 8 weeks; the second (S8-week) group underwent intermittent cigarette smoke inhalation and individual rabbits were killed at 8 weeks; the third (C6-week) group did not undergo cigarette smoke inhalation, and animals were killed at 6 weeks; and the fourth (S6-week) group underwent intermittent smoke inhalation and group-included rabbits were killed at 6 weeks. Subsequent to the animals having been killed, the fusion masses were harvested for a series of studies including manual palpation, biomechanical testing, radiographic examination, and histologic analysis. RESULTS: Six rabbits died shortly after the operation. Of the remaining 34 rabbits, the lumbar spine specimen was harvested for study. Manual palpation, radiographic examination, and histologic analysis of the fusion masses revealed no statistically significant difference in fusion results between the control and the corresponding smoking group killed at either 8 weeks or 6 weeks. Biomechanical testing of the fusion masses also revealed no statistically significant difference in fusion results between the control and the smoking group killed at 8 weeks, although it did indicate that smoking resulted in a 44% decrease in mean flexion stiffness and a 32% decrease in mean extension stiffness among the animals killed at 6 weeks. The former (decrease in flexion stiffness) was statistically significant (p < 0.05). CONCLUSION: The results of the biomechanical testing conducted as a part of the current study demonstrate that acute cigarette smoke inhalation delays but does not prevent the spinal fusion process for rabbits.

Dehydrated form of plasmid expressing basic fibroblast growth factor-polyethylenimine complex is a novel and accurate method for gene transfer to the cornea.

PURPOSE: We describe a novel vector system of nonviral gene transfer into the cornea using a dehydrated form of a plasmid expressing basic fibroblast growth factor-polyethylenimine (p-bFGF-PEI) complex to induce angiogenesis. METHODS: Corneal neovascularization was evaluated in 48 eyes of Sprague-Dawley rats after implantation of a dehydrated form of PEI containing 1 microg green fluorescent protein (p-GFP-PEI; control group), or 10 microg, 1 microg, or 0.1 microg of p-bFGF-PEI introduced by spin vacuum at ambient temperature. Neovascularization was observed and quantified from day 1 to day 45. Eighteen kDa bFGF protein expression was analyzed by Western blot and immunohistochemistry. RESULTS: Limbal vessels began to sprout on day 3 in the p-bFGF-PEI groups. The dehydrated form of the p-bFGF-PEI complex induced dose-dependent corneal neovascularization, which reached a maximum on days 24-30 in the 10 microg bFGF group, days 18-24 in the 1 microg bFGF group, and days 15-21 in 0.1 microg bFGF group, and then regressed progressively. No neovascularization was observed in the GFP group. CONCLUSIONS: The dehydrated form of the p-bFGF-PEI complex is a novel and precise method for controlling the dose, localizing the reagents, and avoiding loss of liquid form during transfection into corneal tissue.

Treatment of empty sella syndrome with ventriculoperitoneal shunt.

A symptomatic empty sella developed in a female patient undergoing bromocriptine therapy for microprolactinoma. Placement of a ventriculoperitoneal shunt dramatically improved the symptoms of headache and blurred vision. The post-operative imaging showed resolution of the empty sella. She was able to resume bromocriptine therapy without recurrence of her previous symptoms and give birth to a baby 20 months later. An MRI 44 months after surgery and on bromocriptine therapy showed no recurrence of the empty sella. We conclude that ventriculoperitoneal shunt may be a simple, and durable treatment for drug induced empty sella and allows resumption of bromocriptine therapy for preexisting microprolactinoma.

Intrathecal gene delivery of glial cell line-derived neurotrophic factor ameliorated paraplegia in rats after spinal ischemia.

Paraplegia is a catastrophic complication of thoracic aortic surgery. At present, there is no effective mean to prevent the ischemia-induced spinal cord trauma. Gene delivery of neurotrophic factors may hold promises for prevention of spinal injury. In the present study, we evaluated the effect of glial cell line-derived neurotrophic factor (GDNF) gene delivery on prevention of the pathological changes due to spinal ischemia. Recombinant adenovirus vectors encoding GDNF (Ad-GDNF) and green fluorescent protein (Ad-GFP) were used for gene transfer studies. Treatment with cobalt chloride induced dose-dependent bcl-2 and synaptophysin downregulation in spinal neuronal cells, which could be effectively reversed by GDNF gene transfer. Intrathecal injection of Ad-GDNF led to maximal GDNF expression in spinal cord within 2-7 days. Thus, after intrathecal administration of adenovirus vectors for 3 days, Sprague-Dawley rats received transient aortic occlusion to induce spinal ischemia and were monitored for behavior deficits. The Ad-GDNF-treated rats showed significantly lower paraplegia rate (40%) than that of Ad-GFP- or saline-treated groups (75-85%; P<0.01). In addition, the Ad-GDNF-treated rats exhibited significantly improved locomotor function comparing with rats of control groups (P<0.001). Histological analysis revealed that GDNF gene delivery profoundly attenuated the infiltration of leukocytes in spinal cord after ischemic insults. Furthermore, GDNF gene delivery prominently attenuated the ischemia-induced neuronal loss in dorsal horn lamina VI-VIII and reduction in synaptophysin expression in spinal cords. In conclusion, GDNF gene transfer confers protection to the neuronal cells and synapses networks, thereby alleviated the paraplegia due to spinal ischemia.

Inhibition of corneal angiogenesis by local application of vasostatin.

PURPOSE: This study was designed to investigate the effects of the locally supplied endogenous angiogenesis inhibitor vasostatin (VS) on corneal angiogenesis. METHODS: Recombinant VS was expressed and purified. The effects of VS on the proliferation of endothelial cells were investigated using the methyl thiazolyl tetrazolium (MTT) assay in the absence or presence of angiogenic factors such as basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). Corneal neovascularization was induced by implantation of hydron pellets containing bFGF in rat corneal micropockets. The potency of VS to inhibit corneal angiogenesis was investigated by incorporation of VS with bFGF in hydron pellets or topical application of VS containing eye drops to rat eyes implanted with bFGF pellets. The extent of corneal neovascularization was evaluated by microscopic and histological analyses. RESULTS: VS potently inhibited the growth of endothelial cells in the absence or presence of angiogenic factors such as bFGF or VEGF. In the rat corneal micropocket assay, concurrent incorporation of VS abolished the bFGF induced neovascularization. When formulated in a methylcellulose eye drop, VS remained intact and functional in a 4 degrees C solution for more than 7 days. Topical application of VS eye drops potently inhibited bFGF induced neovascularization in rat corneas. CONCLUSIONS: The present study effectively demonstrated the potential feasibility of local application of VS for treatment of corneal angiogenesis.

Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats.

AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 microg/h for 5 d. Co-administration of intrathecal roscovitine 1 microg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose-response curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED50 of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

Single versus separate registration for computer-assisted lumbar pedicle screw placement.

STUDY DESIGN: This is a retrospective study conducted to evaluate the efficacy of single versus separate registration in assessing the pedicle screw accuracy in the computer-assisted lumbar spinal instrumentation. OBJECTIVES: To see if separate registration reduced lumbar pedicle screw misplacement. SUMMARY OF BACKGROUND DATA: Computer-assisted spinal instrumentation has been shown to improve pedicle screw installation accuracy, but 2.7% to 8% of screws still perforate the pedicular cortex. Suspected causes include differences in lumbar lordosis between preoperative CT scans and surgery. METHODS: Postoperative radiographs and CT scans were used to assess the accuracy of pedicle screw placement in 47 adult patients following computer-assisted lumbar spinal instrumentation. Twenty-two patients underwent single registration at one level, while the other 25 underwent registration at each level. RESULTS: The time required for a registration procedure on one level was 6 to 8 minutes, while the time required for application of a pedicle screw using computer-assisted techniques was an additional 6 to 10 minutes. The total number of screw placements was 118 in the single registration group and 130 in the separate registration group. In the former group, 85 (72%) pedicle screw placements were categorized as good, 28 (24%) were fair, and 5 (4%) were poor. All five poorly placed screws were placed in the lower lumbar or upper sacral spine with high mobility, and at levels without registration, with one causing root injury. In the latter group, 117 (90%) pedicle screw placements were good and 13 (10%) were fair. The difference in placement was found to be statistically significant (chi2, P = 0.0003). CONCLUSION.: Before the intraoperative real-time CT imaging is widely used, separate registration at each instrumented level during traditional computer-assisted lumbar spinal instrumentation is necessary to enhance the accuracy of screw placement.

Double-blind parallel comparison of multiple doses of apraclonidine, clonidine, and placebo administered intra-articularly to patients undergoing arthroscopic knee surgery.

OBJECTIVE: This clinical study assessed and compared the potential analgesic and adverse effect of IA apraclonidine with IA clonidine. METHODS: Eighty patients scheduled for arthroscopic knee surgery under general anesthesia were randomized to receive, in a double-blind manner, either IA normal saline (group 1), 50 microg IA apraclonidine (group 2), 150 microg IA apraclonidine (group 3), or 150 microg IA clonidine (group 4), all in a volume of 20 mL subsequent to surgery. Visual analog pain scores (VAS), the duration of analgesia as defined by the time to first demand for supplemental analgesics, the subsequent 24-hour consumption of postoperative supplementary analgesics, and patient adverse effects were evaluated. RESULTS: The patients from groups 3 and 4 demonstrated a longer duration of analgesia and used fewer analgesics in the first postoperative 24 hour period compared with group 1 and 2 patients (P < 0.05). The VAS scores corresponding to the periods 1, 2, and 4 hours postoperatively were significantly lower for group 3 than for group 1 patients. The VAS scores at 1 and 4 hours postoperatively were also lower for group 3 than for group 2 patients (P < 0.05). There was no significant difference in the incidence of side effects among the 4 groups. DISCUSSION: The IA application of 150 microg apraclonidine and 150 microg clonidine provide similar degree of postoperative analgesia following knee arthroscopic surgery without any difference in adverse events.

Cranial repair using BMP-2 gene engineered bone marrow stromal cells.

BACKGROUND: Bone grafts, allografts, and biocompatible artificial bone substitutes all have their shortcomings when used for the repair of cranial bone defects. Tissue engineered bone shows promise as an alternative for the repair of these defects. MATERIALS AND METHODS: Rabbit bone marrow mesenchymal stromal cells (MSCs) were separated from iliac crest aspirates and expanded in a monolayer culture 1 month before implantation. These MSCs were then infected with replication-defective adenovirus-human BMP-2 genes 1 week before implantation. Bilateral critical-size cranial defects were created in the animal with removal of osteoinductive periosteum and dura. MSCs were mixed with alginate UP (ultrapure) to form MSC/polymer construct. MSCs used for the control site were infected with adenovirus beta-galactosidase (beta-gal). After 1 week, 6 weeks, and 3 months, five rabbits from each experimental group were sacrificed and the cranial defect site was examined by histology study. RESULTS: Near-complete repair of the large size cranial defects using the tissue engineered MSC/alginate construct was observed. The H&E stain and von Kossa's staining should better regenerate bone at the experiment site. A statistically significant difference in bone formation was noted by 3D CT imaging at 3 months post-BMP-2 treatment of the cranial defects (0.79 +/- 0.06 versus 0.47 +/- 0.05 cm(2), P < 0.001) but not at 6 weeks (0.36 +/- 0.04 versus 0.33 +/- 0.03 cm(2), P = 0.347). CONCLUSIONS: Near-complete repair of large cranial defects can be achieved using tissue engineered bone. The use of newly developed polymers as well as the integration of the stem cell concept with gene medicine is necessary to attain this goal.