Diagnostic yield of computed tomography in the evaluation of unilateral vocal fold palsy.

BACKGROUND: There is a paucity of Asian-based data regarding the diagnostic yield of computed tomography imaging in the initial assessment of idiopathic unilateral vocal fold palsy. OBJECTIVES: To investigate the diagnostic yield of computed tomography in idiopathic unilateral vocal fold palsy cases in an Asian tertiary hospital, and to determine the causative pathologies and positive predictive factors. METHOD: A retrospective chart review was conducted of patients (between 2010 and 2018) with a clinical diagnosis of idiopathic unilateral vocal fold palsy who underwent contrast-enhanced computed tomography of the neck and chest at Tan Tock Seng Hospital, Singapore. RESULTS: The overall computed tomography diagnostic yield was 21 per cent, with malignancy accounting for 63.6 per cent of diagnoses. Degree of vocal fold weakness was the only significant predictor of positive computed tomography findings (11.5 per cent in vocal fold paresis vs 29.1 per cent in vocal fold paralysis, p = 0.025). None of the patients with negative computed tomography findings went on to develop disease after a mean follow up of 14.3 months. CONCLUSION: Computed tomography is a useful initial investigation for idiopathic unilateral vocal fold palsy, particularly in cases with vocal fold paralysis.

Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial.

BACKGROUND: CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC). METHODS: Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07). CONCLUSIONS: CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509). TRIAL REGISTRATION: NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.

Molecular characterization of a variant Ph1 translocation t(9;22;11) (q34;q11;q13) in chronic myelogenous leukemia (CML) reveals the translocation of the 3'-part of BCR gene to the chromosome band 11q13.

We performed cloning and sequence analysis of translocation junctions at 11q- and 22q- (Ph1) chromosomes and the corresponding germline DNAs of a variant Ph1-positive CML with t(9;22;11)(q34;q11;q13). Southern blot analysis using probes for different regions of bcr mapped the translocation break near the 5'-side of bcr exon 4. Cloning, Southern blot analysis and restriction map analysis of both bcr fragments showed that the part of bcr 3'- to the translocation break moved to 11q13. Sequence analysis of the translocation junction on the Ph1 chromosome showed that the translocation break occurred 63 bp upstream of exon 4. Compared to the germline sequence, bcr sequence from the translocated partners showed deletion of seven basepairs at the site of translocation. A probe derived from the 5'-region of the clone isolated from the 11q- chromosome identified clonal rearrangements in the leukemic DNA. Restriction map and sequence analysis showed that this clone consisted of the 3'-half of the glutathione S-transferase Pi (GST-Pi) gene and the 3'-part of bcr. We identified two point mutations in the GST-Pi allele involved in translocation. Northern blot analysis showed that the GST-Pi gene was expressed in the leukemic cells at blast crisis but not at chronic phase; however, no fusion mRNA between GST-Pi and bcr was identified. We did not find any sequence homology between 11q13 DNA and 22q11 DNA around the translocation breakpoints; however, sequences homologous to ALU repeats were identified close to the sites of translocation breaks at 22q11 and 11q13. This study supports our hypothesis that variant Ph1 translocations may occur as primary cytogenetic changes similar to the classical Ph1 translocations.

Measurement of the visual contribution to postural steadiness from the COP movement: methodology and reliability.

We studied the reliability of different measures of the visual contribution to postural steadiness by recording the postural sway during standing with eyes open (EO) or eyes closed (EC). The COP trajectory was recorded in 21 subjects aged 42-61 standing on a firm or foam support. The improvement of postural steadiness due to vision was measured with a higher reliability (i.e. lower intra- and inter-subject variabilities) with the sway velocity V, than with the position RMS. Due to the increase of the variability of V and RMS with their own mean values, we quantified the visual contribution to posture by the stabilization ratio (SR), based on a logarithm transform of V or RMS. As compared to the Romberg quotient (EC/EO), SR improved the reliability of the measurement of the visual contribution to posture within individuals, across subjects, and even across different studies in the literature. Our method led to decrease the inter-subject coefficient of variation of this measurement to about 25%, using a foam support. It leads to a similar accuracy in binocular and monocular vision, and it also applies to the quantification of other non-visual sensory contributions to posture.

Development of an integrated CAD-FEA process for below-knee prosthetic sockets.

BACKGROUND: Computer-aided design and manufacturing has been successfully used in prosthetic applications since 1980s. It simplifies the socket rectification process and improves reproducibility but does not introduce any new principle into socket design. Integrating finite element analysis to CAD will provide a more objective assessment of socket fit and improve the chance of a successful first fitting. METHODS: Current study aims to establish a finite element model generation technique directly from geometrical information of commercial prosthetic CAD workstation. A program developed in-house automatically performs meshing of the stump geometry and assigns suitable material properties, load and boundary conditions to the model. The model was validated by comparing predicted pressure with experimentally measured values for one amputee subject. FINDINGS: The predicted pressure distribution has an root-mean-square error of 8.8 kPa compared to experimental values at 10%, 25% and 50% of the gait cycle. INTERPRETATION: Current method was able to develop a finite element model to predict interface pressure reasonably well and can be integrated with prosthetic CAD system to provide quantitative feedback to the prosthetist in an automated process.

Mesenchymal stem cells in musculoskeletal tissue engineering: a review of recent advances in National University of Singapore.

A key factor in the tissue engineering approach to tissue repair and regeneration is the use of appropriate cells. Mesenchymal stem cells (MSCs) are derived from bone marrow stroma or connective tissues and they have the potential to differentiate into various mesenchymal cell lines in vitro and in vivo. These cells hold great promise for musculoskeletal tissue engineering. This review is based mainly on the work which has been done in the National University of Singapore on the use of MSCs for engineering cartilage, growth plate, bone and tendon/ligament as well as the clinical trail of autologous chondrocyte implantation. It can help to shape future research on musculoskeletal tissue engineering.

Cold extrusion deformation of UHMWPE in total knee replacement prostheses.

The use of metal-backed tibial plates in total knee replacement prostheses can result in the flow of ultra-high molecular weight polyethylene (UHMWPE) from the tibial insert into a cavity on the metal tray surface. A study of the relationship between the thickness of UHMWPE inserts and the amount of cold extrusion is reported here. An attempt was made to correlate the occurrence of cold extrusion with computer-aided analysis. UHMWPE samples of varying thickness, from 3 mm to 10 mm, were placed over cobalt-chrome (Co-Cr) discs. The Co-Cr discs had a 5 mm diameter hole placed centrally to simulate a tibial tray cavity. A cyclic load was applied at 20 Hz through a Co-Cr spherical indentor for a million cycles. The application of cyclic loading on UHMWPE samples resulted in cold-extrusion values comparable to those reported for retrieval analysis studies. Results after fatigue loading show that the samples do not suffer any gross surface damage. A shiny depression was visible at the load application site and the surface roughness value was decreased. The amount of cold extrusion increased with decreasing UHMWPE sample thickness. From the results, a minimum UHMWPE thickness of 12 mm is required if cold extrusion of UHMWPE is to be eliminated.

Effect of pore sizes and cholesterol-lipid solution on the fracture toughness of pure titanium sintered compacts.

Commercial pure titanium has been widely used as an implant material because of its excellent biocompatibility and good ductility. To determine the effect of pore size on the fracture resistance of porous titanium compacts, a series of fracture toughness (KQ) tests were performed on commercial pure titanium powder compacted to 0.17 and 0.62 GPa. Pore sizes ranged from 25 to 103 microns, with porosity between 8.5 and 35%. Two sets of fracture toughness tests using disc-shaped compacts (ASTM E 399-90) were performed, the first in air at 37 degrees C and the second with compacts treated in cholesterol-lipid solution at 37 degrees C. The KQ value of compacts with a smaller mean pore size (ca. 50 microns) was approximately twice that of the compacts with a larger mean pore size (100 microns). The effect of cholesterol-lipid solution treatment was detrimental, perhaps due to preferential lipid absorption by the titanium oxide and/or the presence of chlorides. For the smaller pore size compacts, the KQ values decreased by up to 20%. For the larger pore size compacts, the effect of cholesterol-lipid solution was less significant. Morphologically, compacts with smaller pore size had a predominantly ductile fracture with significantly higher dimple density than the larger pore size compacts.

In vivo mesenchymal cell recruitment by a scaffold loaded with transforming growth factor beta1 and the potential for in situ chondrogenesis.

The objectives of this study were (1) to develop a biphasic implant made of a bioresorbable polymeric scaffold in combination with TGF-beta1-loaded fibrin glue for tissue-engineering applications, and (2) to determine whether the implant made of a polycaprolactone (PCL) scaffold and TGF-beta1-loaded fibrin glue could recruit mesenchymal cells and induce the process of cartilage formation when implanted in ectopic sites. Twenty-four 6-month-old New Zealand White rabbits were used. Scaffolds loaded with various doses of TGF-beta1 in fibrin glue were implanted subcutaneously, intramuscularly, and subperiosteally. The rabbits were killed and implants were removed at 2, 4, and 6 weeks postoperatively. The specimens were subjected to various staining techniques for histological analysis. Light microscopic examination of all specimens revealed that the entire pore space of the scaffolds was filled with various tissues in each group. The entire volume of the scaffolds in the groups loaded with TGF-beta1 and implanted intramuscularly and subcutaneously was populated with mesenchymal cells surrounded with an abundant extracellular matrix and blood vessels. The scaffold loaded with TGF-beta1 and implanted subperiosteally was found to be richly populated with chondrocytes at 2 and 4 weeks and immature bone formation was identified at 6 weeks. We conclude that scaffolds loaded with TGF-beta1 can successfully recruit mesenchymal cells and that chondrogenesis occurred when this construct was implanted subperiosteally.

Hodgkin's disease and non-Hodgkin's lymphoma in an HIV positive patient.

The occurrence of HIV associated non-Hodgkin's lymphoma (NHL) is a well recognized event. HIV associated Hodgkin's disease (HD) has also been observed. A unique patient with both entities is described. The patient was a 29 year old homosexual male who developed clinical IIA nodular sclerosis HD in 1985. He was HIV + with CD4/CD8 = 0.2 and his sister had HD 20 years earlier. He received MOPP and had a complete response. In October 1988 he developed weight loss with an abdominal mass and biopsy revealed diffuse small non-cleaved NHL, with bone marrow involvement. This was his first AIDS associated illness. Probes identified clonally rearranged DNA fragments in the J region of IgH chains and clonal rearrangements in the c-myc gene were also observed but EBV sequences could not be demonstrated. He was treated with m-BACOD but died in March 1989. His course was not complicated by opportunistic infection. Possible etiologies for the HD include his HIV status or shared sibling environment. The development of the NHL may have resulted from HIV infection and/or secondary to his treatment for HD. The relationship between the two lymphomas is uncertain and factors other than HIV exposure and its immune dysfunction may have been causal.

Paired cylindrical interbody cage fit and facetectomy in posterior lumbar interbody fusion in an Asian population.

STUDY DESIGN: The intervertebral disc heights and interfacetal distances of normal lower lumbar segments were measured from MRI scans of 150 male subjects. OBJECTIVES: To investigate the probabilities of paired cylindrical interbody cage placement across the facet joints of the lower lumbar spine in an Asian population with respect to the spinal segmental level, facetectomy, and the restoration of normal intervertebral height. SUMMARY OF BACKGROUND DATA: Cylindrical interbody cage devices often require extensive facetectomy for insertion through a posterior approach in a posterior lumbar interbody fusion (PLIF) procedure. This is because the transverse dimension of a pair of cages could far exceed the interfacetal interval of the lumbar segment. METHODS: One hundred and fifty MRI scans of the lumbosacral spine of male patients between the ages of 18 and 55 years undergoing investigation for low back pain were collected for this study. The interfacetal distances and intervertebral disc heights were measured from transverse and sagittal images, respectively, at L3/L4, L4/L5 and L5/S1. Degenerated discs were not measured. The inner, mid, and outer interfacetal distances were compared with the dimensions of paired cages of 13, 15, and 17 mm in diameter to obtain the proportion of lumbar segments at a particular spinal level that would accommodate paired cages of different diameters and under conditions of varying degrees of facetectomy. RESULTS: Without facetectomy, there was no lumbar segment that could accommodate paired cages as well as restore intervertebral height. With hemi-facetectomy, very few segments at L3/L4 and L4/L5 could fit paired cages. At L5/S1, fewer than 9% of segments could fit paired cages and restore intervertebral heights. The proportion of segments that could accommodate paired cages increased with near-total facetectomy: 25% of L5/S1 segments could accommodate 15-mm cages with restoration of intervertebral heights. CONCLUSIONS: Paired cylindrical cage installation in the majority of patients is likely to require near-total or total facetectomy, with implications for potential segmental instability. Among the three lumbar segments studied, L5/S1 had the highest proportion of segments that could accommodate paired cages and at the same time restore intervertebral height.

Influence of PLIF cage size on lumbar spine stability.

STUDY DESIGN: In vitro biomechanical testing on functional spine units with posterior lumbar interbody fusion cage implants of progressively larger sizes. OBJECTIVES: To determine the influence of increasing cage size on the restoration of spine stability after total facetectomy. SUMMARY OF BACKGROUND DATA: Bilateral insertion of cages in posterior lumbar interbody fusion commonly involves facetectomy. To restore stability with no additional instrumentation, the cages must provide sufficient distraction of the vertebrae and adequate tension in the anulus. The size of cages is therefore an important consideration in posterior lumbar interbody fusion. METHODS: Eight human lumbar functional spine units were obtained and divided into two equal groups; one group underwent bending tests and the other twisting. The functional spinal units were tested intact, after total bilateral facetectomy and with three sets of cages that were progressively larger in size. RESULTS: After facetectomy, the functional spine unit's stiffness reduced significantly from that of the intact spine in extension (48% of intact), lateral bending (25%), and torsion (39%). With the posterior insertion of small cages into the facetectomized functional spine units, only extension stiffness was restored to the intact level, whereas flexion stiffness reduced significantly (41% of intact). The medium cages restored the lateral bending stiffness of the facetectomized functional spine units; only the large cages managed to restore the torsional stiffness. Flexion stiffness of the facetectomized functional spine units with cages remained significantly less than that of the intact spine, regardless of cage size. CONCLUSION: In the facetectomized lumbar spine unit, cage size influences lateral bending and torsional stability.

Linear correlation between axial and lateral bone mineral density of lumbar vertebrae.

The placement of most spinal interbody devices is above the cancellous region of the vertebral bodies. Dual X-ray absorptiometry (DXA) scans of patients are usually taken from the anterior-posterior or the lateral projection. DXA scans taken in vitro from the axial direction would most closely indicate the bone mineral density (BMD) of the bone at this region. So far, in vitro studies have not been conducted to determine the correlation between axial and lateral scans. Because lateral DXA BMD scans are noninvasive and have low radiation dosage, they could be used as a predictive tool to determine the quality of cancellous bone at the centrum of the vertebral bodies, where spinal interbody devices are commonly placed.

Biomechanical strength of non-vascularised and vascularised diaphyseal bone transplants. An experimental study.

We studied the healing and torsional strength of non-vascularised (28) and vascularised (28) sections of tibial diaphyses in 56 cats. Both types of graft achieved fracture union in the same period of time, and at 12 and 16 weeks the non-vascularised grafts were as strong as the vascularised grafts.

A cadaver study of the function of the oblique part of vastus medialis.

Six normal cadaver lower limbs were mounted on a specially designed loading apparatus. Wires were used to simulate the five muscle bellies of the quadriceps, the ratio of their tensions having been determined from that of the anatomical cross-sectional areas of the muscles. A three-camera system was used to track the patella during knee movements from flexion to extension. The patellofemoral contact area was determined by pressure-sensitive film. The limb was loaded with and without tension on the wire which simulated the oblique part of the vastus medialis (VMO). Absence of VMO tension caused the patella to displace laterally (4.2 mm) and increased the load on the lateral patellar facet throughout the range of knee motion. When the tension on the wire simulating vastus lateralis was reduced by 40% to simulate the effect of a lateral release procedure, the abnormal kinematics caused by the absent VMO returned to normal.

Donor site morbidity following resection of the fibula.

Ten adults were studied two to seven years after resection of a fibula for use as a free vascularised bone graft. Six had no symptoms in the donor leg, four had some aching, weakness or paraesthesia and three had definite weakness of the long toe flexors and extensors. All knees and ankles were clinically and radiologically stable, but the distal fibular remnant was osteoporotic in nine patients. Gait analysis of the donor leg and the contralateral normal leg showed definite differences, which could be attributed to weakness of the deep muscles caused by loss of their normal origin and to the change in load transmission through the fibula.

Surface morphology of Asian cadaveric hips.

The joint surfaces of 60 hips obtained from the cadavers of elderly Asians were studied to determine the incidence, the grade and the distribution of both non-progressive (age-related) and progressive degenerative changes. It was observed that in the Asian population of 40 to 90 years of age, non-progressive changes were common, being seen in 66% of the acetabular specimens and 50% of the femoral heads. Only one specimen of the 60 showed unexplained progressive degenerative change. We conclude that primary osteoarthritis of the hip is rare in Asians.

Periprosthetic bone remodelling after cementless total hip replacement. A prospective comparison of two different implant designs.

In a prospective study of 14 patients undergoing total hip replacement we have used dual-energy X-ray absorptiometry (DEXA) to investigate remodelling of the bone around two different designs of cementless femoral prosthesis. The bone mineral density (BMD) was measured at 12-weekly intervals for a year. Eight patients (group A) had a stiff, collarless implant and six (group B) a flexible isoelastic implant. Patients in group A showed a decrease in BMD from 14 weeks after operation. By 12 months, the mean loss in BMD was 27%, both medially and laterally to the proximal part of the implant. Those in group B showed an overall increase in BMD which reached a mean of 12.6% on the lateral side of the distal portion of the implant. Our results support the current concepts of the effects of stem stiffness and flexibility on periprosthetic remodelling.

The effect of submandibular gland removal on testicular and epididymal parameters.

The effect of sialoadenectomy (submandibular gland removal) for four weeks duration was studied in five C3H mice and four sham-operated controls. This preliminary experiment using small numbers of animals indicated that sperm production parameters were lowered in sialoadenectomized animals although there were no significant differences between the sialodenectomized and sham-operated group. In a second experiment using larger numbers of animals, significant differences in testicular weights, epididymal weights, and testis weights were noted. These parameters were reduced only 10-14% from control levels. Epididymal sperm head counts were reduced 10% after sialoadenectomy but the two groups were not significantly different (P less than 0.05). No difference in testicular histology was observed. The present report contrasts to that of Tsutsumi et al. (1986) who indicate that submandibular removal with subsequent depletion of epidermal growth factor (EGF), is extremely deleterious (40-55% decreases in spermatid and sperm content) to the progress spermatogenesis.

Optimization of stacked half-hitch knots for arthroscopic surgery.

PURPOSE: This study was conducted to determine the optimal configuration of stacked half-hitch knots that would give the maximum knot-holding capacity (KHC). TYPE OF STUDY: Mechanical testing study. METHODS: The 2 types of suture materials tested were No. 1 PDS II monofilament and No. 2 Ethibond braided (Ethicon, Somerville, NJ) because these are the 2 most commonly used sutures in arthroscopic surgery. Twelve configurations of stacked half-hitch knots including 2 versions of the Revo knot were tested. Knots were tied between 2 steel hooks 7 mm apart on a manual knot-testing machine. The steel hooks were spread apart to break the knot and the KHC was determined by the peak load recorded on the digital force transducer. Maximum KHC was achieved for No. 1 PDS II sutures by locking the knot with 2 RHAPs (reversing half-hitch on alternate post) and, for No. 2 Ethibond sutures, by locking the knot with 3 RHAPs. Because of the possibility of PDS II sutures unraveling, it is recommended for both No. 1 PDS II and No. 2 Ethibond sutures, that all stacked half-hitches be locked with 3 RHAPs. By adding 1 RHAP to the Revo knot, failure by slippage can be eliminated. RESULTS: The recommended knots tied with braided No. 2 Ethibond sutures were 1.5 times stronger than knots tied with No. 1 PDS II sutures. Although there was variability in the KHC of the recommended knots tied by different surgeons using different knot tiers, the greatest difference in the mean KHC was less than 10%. CONCLUSIONS: Stacked half-hitch knots locked with 3 RHAPs are unlikely to fail by slippage.