Development and validation of a simple, sensitive, selective and stability-indicating RP-UPLC method for the quantitative determination of ritonavir and its related compounds.

A simple, sensitive, selective and reproducible stability-indicating ultra-performance liquid chromatographic method was developed for the quantitative determination of degradation products and process-related impurities of Ritonavir in a pharmaceutical dosage form. Chromatographic separation was achieved on a polar embedded Waters Acquity BEH Shield RP18 (100 × 2.1 mm, 1.7 µm) column thermostated at 50°C under gradient elution by using a binary mixture of potassium dihydrogen phosphate (0.01 M, pH 3.5) and acetonitrile at a flow rate of 0.5 mL/min. Chromatogram was monitored at 240 nm using a photodiode array detector. The drug and its related impurities are eluted within 20 min. To prove the stability-indicating power of the method, the drug was subjected to hydrolytic (acid, alkaline and water), oxidative, photolytic and thermal stress conditions. The unknown degradants were identified by the LC-MS-MS method, which revealed protonated molecular ion peaks [M + H](+) at m/z 551.40 for hydrolytic degradants, and m/z 737.60 and m/z 753.40 for photolytic degradants. A plausible mechanism for the formation of degradation and process impurities was proposed. The performance of the method was validated according to the International Conference on Harmonization guidelines.

Anterior cervical fusion using dense cancellous allografts and dynamic plating.

OBJECTIVE: Dense cancellous grafts provide an open matrix for vascular and cellular penetration for early osseous integration. Thus, they provide a better biological fusion substrate than cortical or corticocancellous grafts. The aim of this study is to evaluate the efficacy of the dense cancellous allografts as a substrate for anterior cervical fusion along with instrumentation. METHODS: This is a retrospective study of 98 patients who underwent anterior cervical discectomy, fusion with dense cancellous allograft bone, and instrumentation using dynamic plating between January 2001 and March 2002. Of these procedures, 60 involved single-level and 38 involved two-level fusions. Subsidence was assessed by plain x-rays at 1, 3, 6, and 12 months and fusion at 3, 6, and 12 months after surgery. Fusion was defined as the appearance of bridging trabecular bone and absence of motion in flexion-extension films. RESULTS: The mean follow-up period was 15 months (range, 12-25 mo). Successful fusion was observed in 70, 84, and 96% of the patients at 3, 6, and 12 months, respectively. The average subsidences for single-level and two-level fusions were 2.0 and 3.2 mm, respectively. No allograft- or hardware-related complications were encountered in our series. CONCLUSION: Dense cancellous allografts are very effective as bone graft substitutes for achieving anterior cervical fusion along with instrumentation. Successful fusion was observed in 70% of our patients at 3 months, with a fusion rate of 96% at 1 year. These allografts provide an effective replacement for autologous grafts in cervical interbody fusion.

Biomechanical comparison of anterior and posterior stabilization methods in atlantoaxial instability.

OBJECT: The authors compared the biomechanical stability of two anterior fixation procedures--anterior C1-2 Harms plate/screw (AHPS) fixation and the anterior C1-2 transarticular screw (ATS) fixation; and two posterior fixation procedures--the posterior C-1 lateral mass combined with C-2 pedicle screw/rod (PLM/APSR) fixation and the posterior C1-2 transarticular screw (PTS) fixation after destabilization. METHODS: Sixteen human cervical spine specimens (Oc-C3) were tested in three-dimensional flexion-extension, axial rotation, and lateral bending motions after destabilization by using an atlantoaxial C1-2 instability model. In each loading mode, moments were applied to a maximum of 1.5 Nm, and the range of motion (ROM), neutral zone (NZ), and elastic zone (EZ) were determined and values compared using the intact spine, the destabilized spine, and the postfixation spine. The AHPS method produced inferior biomechanical results in flexion-extension and lateral bending modes compared with the intact spine. The lateral bending NZ and ROM for this method differed significantly from the other three fixation techniques (p < 0.05), although statistically significant differences were not obtained for all other values of ROM and NZ for the other three procedures. The remaining three methods restored biomechanical stability and improved it over that of the intact spine. CONCLUSIONS: The PLM/APSR fixation method was found to have the highest biomechanical stiffness followed by PTS, ATS, and AHPS fixation. The PLM/APSR fixation and AATS methods can be considered good procedures for stabilizing the atlantoaxial joints, although specific fixation methods are determined by the proper clinical and radiological characteristics in each patient.

Thoracoscopic transdiaphragmatic approach to thoracolumbar junction fractures.

BACKGROUND CONTEXT: Anterior approaches to the thoracocolmbar junction (TLJ) are often required to restore anterior column deficiency after spinal trauma. Conventional open approaches are often associated with significant morbidity, and hence there is a need for a minimally invasive approach to TLJ fractures. PURPOSE: To report the feasibility and effectiveness of the thoracoscopic transdiaphragmatic approach (TTA) in the management of TLJ fractures. STUDY DESIGN: A retrospective analysis of 212 patients undergoing surgery at two institutions by the TTA with neurological outcomes, fusion rates and complications. PATIENT SAMPLE: This is a two-institution study of 212 patients managed by TTA, from Berufsgenossenschaftliche Unfallklinik Marnau, a regional trauma facility located in Murnau, Bavaria, Germany, and from Stanford University, Stanford, California from May 1996 to June 2002. Patient ages ranged from 16 to 75 years (mean, 36 years) and included 158 males and 62 females. OUTCOME MEASURES: The neurological status was assessed by the Frankel Neurological Performance scale pre- and postoperatively. Plain radiographs obtained 1 year postoperatively assessed fusion radiologically. METHODS: All patients underwent spinal decompression, reconstruction and instrumentation by the TTA. Seventy-five patients had anterior instrumentation alone, whereas the remaining 137 had combined anterior and posterior instrumentation. A Z-Plate was used for spinal instrumentation from May 1996 to October 1999 and the MACS-TL system from November 1999 to June 2002. RESULTS: Monosegmental, bisegmental and multisegmental fixations were used in 46%, 48% and 6% of cases, respectively. Follow-up ranged from 12 months to 6 years (mean, 3.9 years). Surgical durations ranged between 70 minutes and 7 hours (mean, 3.5 hours). Successful bony fusion with maintenance of satisfactory spinal alignment was observed in approximately 90% of our patients. Anterior screw loosening was seen in five cases (2.4%), four involving the Z-Plate system and the other involving the MACS-TL system. Three patients (1.4%) required conversion to an open procedure. Access-related complications, such as pleural effusion, pneumothorax and intercostal neuralgia, were seen in 12 patients (5.7%). Three patients (1.4%) had superficial portal infections. We encountered no diaphragmatic herniations. CONCLUSIONS: TTA provides excellent access to the entire TLJ, permitting satisfactory spinal decompression, reconstruction and instrumentation. Diaphragmatic opening and repair can be accomplished safely and effectively without special endoscopic instrumentation. It also precludes the need for retroperitoneoscopic or open thoracoabdominal approaches and thus avoids the associated significant morbidity.

Black disc disease: a commentary.

Internal disc disruption associated with axial back pain but not radicular pain is a disease entity that was recognized about two decades ago as a disorder that could potentially be treated by spinal fusion. In this article the authors describe the clinical syndrome, magnetic resonance imaging and discography findings of pathophysiological pain generation, and the available surgical options. Based on the current understanding of this disease entity, the optimum surgical procedure entails radical discectomy, anterior column support, adequate amounts of auto- or allograft bone, bone extenders and enhancers, and rigid stabilization of the motion segment.

Management of strut graft failure in anterior cervical spine surgery.

Although successfully used, long strut grafts are vulnerable to dislodgment, displacement, fracture, and nonunion, which can require revision surgery; thus, meticulous preparation of the vertebral endplate along with exact sizing and harvesting of the bone graft with plating are essential for successful outcomes. Biomechanical data and previous clinical studies support the addition of posterior fusion and fixation following multilevel (more than two-level) corpectomy. The additional posterior instrumentation moves the instantaneous axis of rotation posteriorly, thus approximating its normal location in the posterior vertebral body (VB). Biomechanically, this protects the graft from excessive loads while in extension and explains the clinical success of circumferential instrumentation for long-segment corpectomy reconstructions. If strut fracture occurs with minimal displacement and the graft position is still satisfactory, application of a halo vest and judicious observation are recommended. Significant displacement, kyphosis, or loss of contact of the graft and VB require revision surgery. In patients requiring revision surgery for nonunion, placement of fibular autograft or allograft with use of bone morphogenetic protein is likely to be beneficial. If questions remain regarding bone quality or construct stability, the supplemental use of posterior stabilization is recommended. Various surgical approaches have been advocated for treatment of symptomatic anterior cervical pseudarthroses or nonunion. It remains controversial as to whether the anterior or posterior approach is best. Adequate understanding of the graft and implant biomechanics are essential for a successful outcome.

Vertebral body replacement with an expandable cage for reconstruction after spinal tumor resection.

OBJECT: The authors report their clinical experience with expandable cages used to stabilize the spine after vertebrectomy. The objectives of surgical treatment for spine tumors include a decrease in pain, decompression of the neural elements, mechanical stabilization of the spine, and wide resection to gain local control of certain primary tumors. Most of the lesions occur in the anterior column or vertebral body (VB). Anterior column defects following resection of VBs require surgical restoration of anterior column support. Recently, various expandable cages have been developed and used clinically for VB replacement (VBR). METHODS: Between January 2001 and June 2003, the authors treated 15 patients who presented with primary spinal tumors and metastatic lesions from remote sites. All patients underwent vertebrectomy, VBR with an expandable cage, and anterior instrumentation with or without posterior instrumentation, depending on the stability of the involved segment. The correction of kyphotic angle was achieved at an average of 20 degrees. Pain scores according to the visual analog scale decreased from 8.4 to 5.2 at the last follow-up review. Patients whose Frankel neurological grade was below D attained at least a one-grade improvement after surgery. All patients achieved immediate stability postsurgery and there were no significant complications related to the expandable cage. CONCLUSIONS: The advantage of the expandable cage is that it is easy to use because it permits optimal fit and correction of the deformity by in vivo expansion of the device. These results are promising, but long-term follow up is required.

Surgical techniques for total sacrectomy and spinopelvic reconstruction.

The surgical management of sacral tumors requires partial or total sacrectomy and spinopelvic reconstruction. These lesions present a great surgical challenge, because most spine surgeons are unfamiliar with the techniques required for these procedures. The authors describe a step-by-step operative technique and provide several illustrations. Total sacrectomy is performed by sequential anterior and posterior approaches that involve a rectus abdominis pullthrough pedicle flap reconstruction. The anterior procedure is an intraperitoneal approach used to expose the anterior aspect of the tumor, to ligate the main tumor vessels, and to conduct an anterior partial sacrectomy. After this, the rectus abdominis myocutaneous flap, based on the inferior epigastric vessel, is prepared, and a posterior sacrectomy is performed, dividing all sacral nerve roots in the thecal sac. After complete en bloc extirpation of the sacrum with tumor, spinopelvic reconstruction and closure with a myocutaneous flap are performed. Spinopelvic reconstruction is undertaken using a modified Galveston technique or double iliac screw fixation combined with posterior lumbar segmental fixation. These provide a long lever arm within the ilium to counteract the forces exerted by the lumbar spine. Understanding the nature of the disease as well as the biomechanics of the lumbosacral pelvic area and spinopelvic fixation will help surgeons select the appropriate treatment for sacral tumors.

Clapeyron slope reversal in the melting curve of AuGa2 at 5.5 GPa.

We use x-ray diffraction in a resistively heated diamond anvil cell to extend the melting curve of AuGa2 beyond its minimum at 5.5 GPa and 720 K, and to constrain the high-temperature phase boundaries between cubic (fluorite structure), orthorhombic (cottunite structure) and monoclinic phases. We document a large change in Clapeyron slope that coincides with the transitions from cubic to lower symmetry phases, showing that a structural transition is the direct cause of the change in slope. In addition, moderate (~30 K) to large (90 K) hysteresis is detected between melting and freezing, from which we infer that at high pressures, AuGa2 crystals can remain in a metastable state at more than 5% above the thermodynamic melting temperature.

Pharmacognosy of leaves of wrightia tinctoria R. Br.

Wrightia tinctora is a tree widely used by the peoples of Tamil Nadu as a traditional medicine for pain and inflammations. Latex form the plant especially from leaves is directly applied on inflammation. This plant is very closely related to other species of Wrightia and hence pharmacognostical and preliminary phytochemical studies of Wrightia tinctoria leaves were carried out.