Comparison of angled versus AP view radiography for post-operative evaluation of lumbosacral spondylolisthesis: a cadaveric study

Background  The objective of this study was to investigate if angled radiographic views of the L5-S1 junction result in quantitatively better images in patients with lumbosacral spondylolisthesis compared to conventional AP view. Methods  Grade I lumbosacral spondylolisthesis was simulated in cadaveric specimens and repaired using pedicle screws and posterolateral bone grafting. Angled view AP radiographs were taken at different angles and analyzed at both grade I spondylolisthesis and complete reduction (to normal). Results  The results indicated that angled view radiographs provide better visualization of intervertebral disc height, area, and posterolateral bone graft area compared with true AP views. The optimal view was at 40° for grade I spondylolisthesis, and at 25°–35° for complete reduction. Conclusion  In addition to the dynamic radiographs currently used for evaluation of patients post-spondylolisthesis repair, an additional angled view radiograph (at 40° or 25–35°) is recommended to evaluate intervertebral disc height, intervertebral area, bone graft area, and pedicle screw position.     

Morphological changes in the cervical intervertebral foramen dimensions with unilateral facet joint dislocation

Background

Many investigators have conducted studies to determine the biomechanics, causes, complications and treatment of unilateral facet joint dislocation in the cervical spine. However, there is no quantitative data available on morphological changes in the intervertebral foramen of the cervical spine following unilateral facet joint dislocation. These data are important to understand the cause of neurological compromise following unilateral facet joint dislocation.

Methods

Eight embalmed human cadaver cervical spine specimens ranging from level C1-T1 were used. The nerve roots of these specimens at C5-C6 level were marked by wrapping a 0.12 mm diameter wire around them. Unilateral facet dislocation at C5-C6 level was simulated by serially sectioning the corresponding ligamentous structures. A CT scan of the specimens was obtained before and after the dislocation was simulated. A sagittal plane through the centre of the pedicle and facet joint was constructed and used for measurement. The height and area of the intervertebral foramen, the facet joint space, nerve root diameter and area, and vertebral alignment both before and after dislocation were evaluated.

Results

The intervertebral foramen area changed from 50.72 ± 0.88 mm² to 67.82 ± 4.77 mm² on the non-dislocated side and from 41.39 ± 1.11 mm² to 113.77 ± 5.65 mm² on the dislocated side. The foraminal heights changed from 9.02 ± 0.30 mm to 10.52 ± 0.50 mm on the non-dislocated side and 10.43 ± 0.50 mm to 17.04 ± 0.96 mm on the dislocated side. The facet space area in the sagittal plane changed from 6.80 ± 0.80 mm² to 40.02 ± 1.40 mm² on the non-dislocated side. The C-5 anterior displacement showed a great change from 0 mm to 5.40 ± 0.24 mm on the non-dislocated side and from 0 mm to 3.42 ± 0.20 mm on the dislocated side. Neither of the nerve roots on either side showed a significant change in size.

Conclusions

The lack of change in nerve root area indicates that the associated nerve injury with unilateral facet joint dislocation is probably due to distraction rather than due to direct nerve root compression.     

Doxycycline administration improves fascial interface in hernia repair

Background

Despite improvements in ventral hernia repair techniques, their recurrence rates are unacceptably high. Increased levels of matrix metalloproteinases (MMPs) and reduced collagen-1 to -3 ratios are implicated in incisional hernia formation. We have recently shown doxycycline treatment for 4 wk after hernia repair reduced MMP levels, significantly increased collagen-1 to -3 ratios, and increased tensile strength of repaired interface fascia. However, this increase was not statistically significant. In this study, we extended treatment duration to determine whether this would impact the tensile strength of the repaired interface fascia.

Materials and methods

Thirty-two male Sprague–Dawley rats underwent incision hernia creation and subsequent repair with polypropylene mesh. The animals received either saline (n = 16) or doxycycline (n = 16) beginning from 1 day before hernia repair until the end of survival time of 6 wk (n = 16) or 12 wk (n = 16). Tissue samples were investigated for MMPs and collagen subtypes using Western blot procedures, and tensiometric analysis was performed.

Results

At both 6 and 12 wk after hernia repair, the tensiometric strength of doxycycline-treated mesh to fascia interface (MFI) tissue showed a statistically significant increase when compared with untreated control MFI. In both groups, collagen-1, -2, and -3 ratios were remarkably increased in doxycycline-treated MFI. At 6 wk, the doxycycline-treated MFI group showed a significant decrease in MMP-2, an increase in MMP-3, and no change in MMP-9. At 12 wk, MMP-9 showed a remarkable reduction, whereas MMP-2 and -3 protein levels increased in the doxycycline-treated MFI group.

Conclusions

Doxycycline administration results in significantly improved strength of repaired fascial interface tissue along with a remarkable increase in collagen-1, -2, and -3 ratios.     

The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films

Films containing polyethylene oxide (PEO) and a model drug, either guaifenesin (GFN) or ketoprofen (KTP), were prepared by hot-melt extrusion. The thermal properties of the hot-melt extruded films were investigated using differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) was used to examine the surface morphology of the films, and wide angle X-ray diffraction (XRD) was used to investigate the crystalline properties of the polymer, drugs and physical mixtures as well as the solid state structure of the films. The stability of the polymer was studied using gel permeation chromatography. The mechanical properties, including percent elongation and tensile strength of the films, were determined on an Instron according to American Society for Testing Materials (ASTM) procedures. The Hansen solubility parameter was calculated using the Hoftyzer or van Krevelen method to estimate the likelihood of drug–polymer miscibility. Both GFN and KTP were stable during the extrusion process. Melting points corresponding to the crystalline drugs were not observed in the films. Crystallization of GFN on the surface of the film was observed at all concentrations studied, however KTP crystallization did not occur until reaching the 15% level. Guaifenesin and ketoprofen were found to decrease drive load, increase PEO stability and plasticize the polymer during extrusion. The Hansen solubility parameters predicted miscibility between PEO and KTP and poor miscibility between PEO and GFN. The predictions of the solubility parameters were in agreement with the XRD and SEM results. The percent elongation decreased with increasing GFN concentrations and significantly increased with increasing levels of KTP. Both GFN and KTP decreased the tensile strength of the extruded film.     

Off-line and on-line measurements of drug-loaded hot-melt extruded films using Raman spectroscopy

The objective of this study was to investigate the use of Raman spectroscopy for the quantitative and qualitative analysis of an active ingredient in hot-melt extruded film formulations. Clotrimazole and ketoprofen were used as the active pharmaceutical ingredients (APIs) in the subject formulations. Films were prepared with contents varying from 1 to 20% of the respective API. Raman spectroscopy was used to quantify these APIs, both off-line and on-line. The spectral data were also used to ascertain the physical status of these APIs in the formulations. For off-line analysis, the films were cut into small rectangles, and the amount of the API was measured using a fiber optic probe equipped with a non-contact optic (NCO). For on-line analysis, real-time measurements were accomplished by fixing the probe over the extruded film for continuous data collection. Raman spectroscopy can be a convenient alternative to HPLC and other techniques currently employed for the quantification of the API in these formulations. Because Raman is also sensitive to changes in crystallinity, employment of the technique provided additional information to deduce the crystalline status of the API. The results reported in this paper suggest the suitability of Raman for PAT applications because of the on-line capability.     

Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute.

Transdermal drug delivery systems (TDDS), also known as "patches," are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. In the Drug Quality Reporting System (DQRS), the United States Food and Drug Administration (FDA) has received numerous reports of "adhesion lacking" for transdermal drug delivery systems. This article provides an overview of types of transdermals, their anatomy, the role of adhesion, the possible adhesion failure modes and how adhesion can be measured. Excerpts from FDA reports on the lack of adhesion of transdermal system products are presented. Pros and cons of in vitro techniques, such as peel adhesion, tack and shear strength, in vivo techniques used to evaluate adhesive properties are discussed. To see a decrease in "adhesion lacking" reports, adhesion needs to become an important design parameter and suitable methods need to be available to assess quality and in vivo performance. This article provides a framework for further discussion and scientific work to improve transdermal adhesive performance.     

Rational design and development of colon-specific prodrugs

Earlier colon was considered as a black-box, acting as a site for production and temporary storage of excreta and responsible for absorption of electrolytes and water. But, with the discovery of sulfasalazine as colon-specific prodrug, the promising and challenging issue of treating local pathologies was presented with colon as an organ of significance for target-specific delivery of drugs. The need and desirable attributes of colon-specific drug delivery systems have been well recognized, extensively explored and documented in the literature. The success of a colon-specific prodrug depends on its rational design and understanding the demands of the organ to be targeted and the delivery system to be developed. The present review mainly focuses on anatomy/physiology of colon, colonic microbiota, enzymatic set up of colon, pathophysiology of local diseases of colon, factors, obstacles and rationale for designing colon specific drug delivery system, various targets, potential drug candidates and novel colon-targeting carriers along with varied linkages that could be explored, merits and demerits of this design and recent trends in this field. Brief review of methodologies for characterization and in vitro/in vivo release studies is presented. The available animal models with quantifying parameters for evaluating colon-targeting potential and effectiveness of the colon-specific prodrugs for inflammatory bowel disease is also included in this review.