Early onset vitreous amyloidosis in familial amyloidotic polyneuropathy with a transthyretin Glu54Gly mutation is associated with elevated vitreous VEGF.

AIM: To report the early vitreous involvement in a rare familial amyloidotic polyneuropathy (FAP) mutation and associated vitreous vascular endothelial growth factor (VEGF) levels. DESIGN: Observational case series. METHODS: Review of clinical, pathological, photographic, and angiographic records of two FAP siblings with severe vitreous involvement. Laboratory ELISA analysis of vitreous samples for VEGF, and DNA sequence analysis of peripheral blood for transthyretin (TTR) mutational analysis. RESULTS: Two patients underwent 25-gauge vitrectomy in three eyes with marked improvement of visual acuity. Neovascularisation seen intraoperatively responded to endolaser. Analysis of vitrectomy samples for VEGF showed raised levels in all three specimens. Mutational analysis revealed an isolated Glu54Gly mutation in the transthyretin gene. CONCLUSIONS: Early involvement of the vitreous occurs in a rare transthyretin mutation of FAP, with increased vitreous levels of VEGF.

Linezolid-induced optic neuropathy: a mitochondrial disorder?

We report a case of bilateral mitochondrial optic neuropathies secondary to long-term linezolid treatment, show the nature of recovery, review the findings in the literature and propose a potential mitochondrial mechanism for linezolid-induced mitochondrial optic neuropathy. This is an observational case report and literature review with presentation of the clinical course of linezolid mitochondrial optic neuropathies through clinical and psychophysical documentation. Main outcome measures included: visual acuity, funduscopical examinations and peripapillary retinal nerve fibre layer (PRNFL) optical coherence tomography (OCT). A 6-year-old boy presented with bilateral optic neuropathies secondary to 1 year of linezolid treatment for osteomyelitis of the mandible. On presentation, visual acuities were 20/400 in both eyes, with considerable optic disc oedema, hyperaemia and PRNFL swelling confirmed by OCT. 2 weeks after the discontinuation of linezolid, visual acuities returned to 20/25 in both eyes, with reduction in the optic disc oedema, hyperaemia and PRNFL swelling. 3 months after the discontinuation of linezolid treatment, visual acuities were stable at 20/20 in both eyes, with a marked decrease in PRNFL swelling confirmed by OCT, and the development of mild temporal optic disc pallor in both eyes. Doctors should be aware of impairments of vision among patients on long-term linezolid treatment and promptly discontinue treatment to prevent irreversible vision loss. The development and resolution of bilateral optic neuropathies with considerable PRNFL swelling in this patient provide insight into the more general rubric of mitochondrial optic neuropathies.

Bilateral symmetry of the human metacarpal: implications for sample size calculations.

OBJECTIVE: The aim of this study was to assess the three-dimensional mechanical symmetry of the human second metacarpal and provide sample size estimates for future mechanical intervention studies of the metacarpal. DESIGN: Bone densitometry and digital image analysis were used to assess the morphometric, geometric and densitometric symmetry of the second human metacarpal. BACKGROUND: An assessment of the left-right mechanical symmetry of the human metacarpal is important in considering the suitability of using the contralateral metacarpal as a control and in providing sample size calculations for future studies involving a mechanical intervention to the metacarpal such as implantation of a metacarpophalangeal prosthesis. METHODS: Metaphyseal sectional areas, diaphyseal cortical sectional areas, second moments of area, average periosteal and medullary radii and bone densities were measured at nine transverse levels for each of seven pairs of index metacarpals using computed tomography and bone densitometry. Polar Fourier regression was used to assess the morphometry of sectional periosteal and endosteal boundaries. Differences between clinically important left-right parameters were assessed. RESULTS: Mean differences between clinically important left-right parameters were small (<3%) and similar to the degree of experimental precision. There were strong significant left-right correlations for the morphometric, geometric and densitometric parameters considered, indicating a high degree of bilateral mechanical symmetry. CONCLUSIONS: The contralateral bone is a suitable control for mechanical intervention studies of the human metacarpal, and the use of bilateral pairing results in an important reduction in sample size. RELEVANCE: Responses to mechanical interventions on the human metacarpal, such as implantation of a metacarpophalangeal prosthesis, are generally unknown. The degree of left-right mechanical symmetry in the human metacarpal provides a measure of the advantage of using paired design studies to address these questions.

Validation of a finite element model of the human metacarpal.

Implant loosening and mechanical failure of components are frequently reported following metacarpophalangeal (MCP) joint replacement. Studies of the mechanical environment of the MCP implant-bone construct are rare. The objective of this study was to evaluate the predictive ability of a finite element model of the intact second human metacarpal to provide a validated baseline for further mechanical studies. A right index human metacarpal was subjected to torsion and combined axial/bending loading using strain gauge (SG) and 3D finite element (FE) analysis. Four different representations of bone material properties were considered. Regression analyses were performed comparing maximum and minimum principal surface strains taken from the SG and FE models. Regression slopes close to unity and high correlation coefficients were found when the diaphyseal cortical shell was modelled as anisotropic and cancellous bone properties were derived from quantitative computed tomography. The inclusion of anisotropy for cortical bone was strongly influential in producing high model validity whereas variation in methods of assigning stiffness to cancellous bone had only a minor influence. The validated FE model provides a tool for future investigations of current and novel MCP joint prostheses.

Cement penetration and stiffness of the cement-bone composite in the proximal tibia in a porcine model.

PURPOSE: To assess the stiffness of the cement bone composite and the depth and uniformity of cement penetration into the surface of the tibial component during total knee reconstruction in a porcine model. METHODS: The effectiveness of 3 protocols were compared: 2 commonly used cementing techniques-finger-packing of cement on the cut surface followed by impaction, and coating of the undersurface of the prosthesis with cement followed by impaction-and a new method using a tibial cement-pressurising device. Cement penetration was measured by computed tomography; stiffness was determined by hydraulic penetration testing. RESULTS: Cement penetration at a depth of 1 mm was significantly greater following coating the undersurface of the prosthesis than following finger-packing (p=0.008). There was no significant difference at deeper levels or between the tibial-pressurising device group and either of the 2 other groups at any level (p>0.3 in all cases). Differences in surface stiffness by tibial plateau region were found in tibiae that had been cemented using finger-packing and in those that had had their undersurface coated, but not in tibiae that had been cemented using the tibial-pressurising device. CONCLUSION: The tibial cement-pressurising device eliminated regional differences in stiffness seen with other cementing methods. Elimination of these differences by using this device should reduce micromotion and the incidence of aseptic loosening of tibial base plates in total knee arthroplasty.

Changing incidence of primary total hip arthroplasty and total knee arthroplasty for primary osteoarthritis.

This study reports on the incidence of primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) for primary osteoarthritis in Australia. Age-specific and gender-specific numbers for Australia, 1994 through 1998, and South Australia, 1988 through 1998, were obtained. Incidences were calculated per 100,000 population. In Australia, primary THA increased from 50.9/10(5) (1994) to 60.9/10(5) (1998). TKA increased from 56.4/10(5) to 76.8/10(5). Stratified by age and gender, changes in incidence for South Australia with respect to time were tested using regression analysis. South Australia showed a significant increase in the overall incidence of THA (P=.012) and TKA (P<.001), although this was not uniform across all age groups. No significant gender differences were found. The incidence of THA is increasing, and the incidence of TKA is increasing at a greater rate.

Mechanical and pathologic consequences of induced concentric anular tears in an ovine model.

STUDY DESIGN: Relations between induced concentric tears in the sheep disc and the mechanics of the intervertebral joint and vertebral body bone were analyzed. OBJECTIVE: To examine the effect of concentric disc tears on the mechanics of the spine. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc results in changes to the mechanics and morphology of the spine, but the effect of concentric disc tears is unknown. METHODS: In this study, 48 merino wethers were subjected to surgery, and discs were randomly selected for either a needlestick injury or induction of a concentric tear in the anterior and left anterolateral anulus. Sheep were randomly assigned to groups for killing at 0, 1, 3, 6, 12, and 18 months. From each sheep, two spine segments were mechanically tested: one with a needlestick injury and one with a concentric tear. Macroscopic disc morphology was assessed by three axial slices of the disc. Sagittal bone slices were taken from cranial and caudal vertebral bodies for histologic analysis. RESULTS: Induced concentric tears decrease the stiffness of intact spine segments in left bending and the disc alone in flexion. In all other mechanical tests, the needlestick injury had the same effect as the induced concentric tear. In the isolated disc, the disc stiffness at 6 months was increased for right bending, as compared with the response at 1 month. This was associated with increased anterior lamellar thickening and increased vertebral body bone volume fraction. CONCLUSIONS: Concentric tears and needlestick injury in the anterior anulus lead to mechanical changes in the disc and both anular lamellar thickness and vertebral body bone volume fraction. A needlestick injury through the anulus parallel to the lamellae produces progressive damage.

Comparison of torsional strengths of bioabsorbable screws for anterior cruciate ligament reconstruction.

The goals of this study were to evaluate torsional strength and modes of failure in commercially available bioabsorbable interference screws and to test the effect of screw diameter on torsional strength when screws become jammed during insertion. We tested the Arthrex, BioScrew, Endo-Fix, Phantom, and Sysorb screws, all 20 mm in length. Four major modes of failure were encountered. Analysis of variance revealed that both screw type and diameter had a significant effect on failure torque. The Endo-Fix 7-mm screw had the lowest failure torque (1.07 +/- 0.18 N x m) and the Sysorb 8-mm screw had the highest (5.23 +/- 0.24 N x m). The Sysorb was significantly stronger than all the other screws. The failure torques were within the range that has been reported for manual screw insertion. We concluded that technical factors, which can affect insertion torque, assume particular importance with the use of bioabsorbable interference screws.

Characterization and applications of etched chemically modified capillaries for open-tubular capillary electrochromatography.

In this article, the effects of the stationary phase, buffer pH, organic modifier type, organic modifier composition, applied voltage, and temperature on the migration of several synthetic peptides in etched chemically modified open-tubular capillaries are discussed. With these solutes, migration is due to two effects: electrophoretic mobility and solute/bonded phase interactions. In addition, relative migration rates are evaluated for the peptide samples as a function of these experimental variables in order to determine which parameters might be useful for optimizing separations in open-tubular capillary electrochromatography (OTCEC). Some examples of synthetic peptide separations are presented where the sample contains a major component and several minor species, demonstrating how the resolution of these mixtures can be affected by the appropriate choice of experimental variables.

Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10q.

The organization of centromeric heterochromatin has been established in a number of eucaryotes but remains poorly defined in human. Here we present 1025 kb of contiguous human genomic sequence which links pericentromeric satellites to the RET proto-oncogene in 10q11.2 and is presumed to span the transition from centric heterochromatin to euchromatin on this chromosome arm. Two distinct domains can be defined within the sequence. The proximal approximately 240 kb consists of arrays of satellites and other tandem repeats separated by tracts of complex sequence which have evolved by pericentromeric-directed duplication. Analysis of 32 human paralogues of these sequences indicates that most terminate at or within repeat arrays, implicating these repeats in the interchromosomal duplication process. Corroborative PCR-based analyses establish a genome-wide correlation between the distribution of these paralogues and the distribution of satellite families present in 10q11. In contrast, the distal approximately 780 kb contains few tandem repeats and is largely chromosome specific. However, a minimum of three independent intrachromosomal duplication events have resulted in >370 kb of this sequence sharing >90% identity with sequences on 10p. Using computer-based analyses and RT-PCR we confirm the presence of three genes within the sequence, ZNF11/33B, KIAA0187 and RET, in addition to five transcripts of unknown structure. All of these transcribed sequences map distal to the satellite arrays. The boundary between satellite-rich interchromosomally duplicated DNA and chromosome-specific DNA therefore appears to define a transition from pericentromeric heterochromatin to euchromatin on the long arm of this chromosome.

Improvement in physician's office laboratory practices, 1989-1994.

BACKGROUND: In 1986 and 1989, the Centers for Disease Control and Prevention sponsored institutes on Critical Issues in Health Laboratory Practice. It was noted during the institutes that physician's office laboratories were a rapidly emerging site for clinical laboratory testing, yet no comprehensive data were available regarding the practice of clinical laboratory medicine in physician's office laboratories. As a mechanism to begin addressing this void, the Centers for Disease Control and Prevention added questions on clinical laboratory practice to the National Ambulatory Medical Care Survey, a national probability sample of ambulatory care provided by office-based physicians. Data were collected for survey years 1989, 1991, 1993, and 1994. METHODS: Each survey was conducted among a nationally representative, random sample of office-based physicians who provide ambulatory patient care. Sample physicians were enlisted using both mail and telephone contacts. Clinical laboratory data were obtained via telephone by trained field representatives. Weighted univariate and multivariate analyses were performed on responses from each of the 4 survey years. Analyses were repeated after combining survey responses from years 1989 and 1991 and 1993 and 1994 as representative of physician's office laboratory practices before and after implementation of the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) final rule in 1992. RESULTS: Quality laboratory practice indicators showed significant increases during the study interval, with implementation of the CLIA '88 final rule in 1992 playing a pivotal role. Relative to 1992, enrollment in proficiency testing programs increased from 32.4% to 52.7% (P<.001), use of daily quality control samples increased from 79.2% to 89.0% (P<.001), and use of daily quality control with written instructions for action following a questionable quality control result (quality control with action step documentation) increased from 62.6% to 77.2% (P<.001). The presence of a medical technologist or technician in the office laboratory was also significantly and independently associated with each of the quality indicators. Although the percentage of physician's offices performing on-site testing decreased from 56% to 45% during the survey interval, overall testing volume appeared unchanged. CONCLUSIONS: The quality of clinical laboratory practice in physician's office laboratories improved during the study interval (1989-1994) as measured by the quality indicators used in the study. The association of this improvement with implementation of the CLIA '88 final rule and the presence of a trained laboratory professional in the testing site indicate the importance of minimum practice standards and professional expertise in ensuring use of quality laboratory practices. Overall test volume appeared to be stable despite a decreased proportion of physician's offices at which on-site testing was performed.

Hip fracture rates in South Australia: into the next century.

BACKGROUND: Fractures of the femoral neck already represent a major public health problem in Australia. This situation is set to worsen as the population ages. The present study estimates the number of patients over 50 years of age with femoral neck fractures that is expected to impact on the South Australian healthcare service into the next century. METHODS: Population projections from the Australian Bureau of Statistics 1996 census were combined with age- and gender-specific incidence rates for fractures of the femoral neck for persons over the age of 50 in South Australia. Projections for the expected number of hip fractures in this State were then calculated. RESULTS: Assuming there are no changes in the age- and gender-specific incidence of fracture rates, the number of fractures in South Australia is estimated to increase by approximately 66% by the year 2021 and 190% by 2051. CONCLUSION: Based on the population projections and the assumption that conditions contributing to hip fractures remain constant, the number of fractured neck of femurs will increase in far greater proportion than the overall population in the next century. The results of the present study indicate the serious implications for the South Australian healthcare system if there is no reduction in incidence rates.

Biomechanical analysis of the Medoff sliding plate.

BACKGROUND: A new device for fixation of hip fractures the Medoff plate was biomechanically tested and compared with the Ambi plate and Gamma nail. METHODS: Six pairs of human cadaveric femurs were used. The characteristics evaluated were structural stiffness, strain distribution, and modes of failure. Results were compared with the Ambi plate and Gamma nail biomechanical studies from a previous study that used the same methods. RESULTS: The Medoff plate was stiffer than the other two implants for intertrochanteric fractures, and for segmental subtrochanteric fracture. The Medoff plate was more load sharing than the other implants in these fracture configurations. The mean load to failure was lower than for the Ambi plate or the Gamma nail. CONCLUSION: The Medoff plate is a better load-sharing device than the Ambi (DHS) or Gamma nail systems. The main concern is its structural weakness. The implant failed at loads 50% less than other devices. The greatest risk of implant failure is with unstable subtrochanteric fractures.

Hip fracture treatments--what happens to patients from residential care?

Hip fractures are a growing problem and new models of care have been called for. However, patients from residential care are rarely considered in these discussions. Hip fracture is a common serious problem for older people in residential care with profound effects on subsequent mobility and quality-of-life. There are no Australian data documenting differences in hospital treatments offered to patients from the community and residential care to inform discussions. In a prospective audit we describe the treatment and 4 month outcomes of patients with fractured hips who were admitted to Flinders Medical Centre in South Australia from the community and residential care between August 1998 and June 1999. Information was collected on prefracture health, types of surgical and rehabilitation treatments and dependency. Of the 215 older adults who were admitted during this time, 183 agreed to participate (119 from community and 64 from residential care). Surgical management of the fracture was not affected by admission accommodation. Those from residential care had short hospital stays, less rehabilitation and access to physiotherapy. Although 61% of those from residential care were classified as independently mobile prefracture, by 4 months this had declined to 32% of survivors. Strategies to improve outcomes in those from residential care include: early identification of those walking independently prefracture with assessment by rehabilitation teams. Inclusion of liaison with community therapists in the clinical pathway and in selected cases use of 'rehabilitation at home' services to provide physiotherapy services should be considered.

Laboratory performance in HTLV-I/II analysis.

BACKGROUND: Since 1989, the CDC's Model Performance Evaluation Program has shipped samples to voluntary participant laboratories that test for HTLV antibodies. Each laboratory tests the well-characterized samples, reports the results, and provides information about its testing practices. The data from 15 performance survey periods are reported here. STUDY DESIGN AND METHODS: Multiple logistic regression was used to analyze all data from 15 survey periods from 1989 through 1996. RESULTS: The mean analytic sensitivity for EIA was 99.2 percent per survey period (range, 96-100%), the mean analytic specificity was 97.8 percent (75.6-100%), and the overall accuracy was 88.8 percent (63.8-100%). The mean analytic sensitivity for Western blot was 88.8 percent (75.6-100%); the mean analytic specificity was 95.7 percent (86.7-100%), and the overall accuracy was 91.1 percent (78.1-100%). CONCLUSIONS: Statistical analyses suggested associations between performance and both the retroviral serologic status of the sample and the analytical testing method. Western blot accuracy was associated with weekly testing volume. In early survey periods, performance problems were noted in the analysis of samples from donors with concomitant HTLV and HIV infections and those from donors who were positive for HTLV-II. Technological developments in test methods, such as the addition of recombinant antigens, appeared to have improved the laboratory performance of specific testing methods.

Do proficiency test results correlate with the work performance of screeners who screen Papanicolaou smears?

We rescreened Papanicolaou smear slides from 40,245 women, which had been examined by 81 cytology screeners, scored the screeners' work performance, and compared these scores with the results of the screeners' performance on glass slide and computer-based proficiency tests. All diagnoses (i.e., from the proficiency tests, the original slides, and the rescreened slides) were classified in the 4 diagnostic categories specified in the Clinical Laboratory Improvement Amendments. The rescreening scores were standardized to account for different distributions of abnormalities in the proficiency tests and rescreened slides. We compared a standardized score with the proficiency test scores. Of the cases, 91% were categorized as normal, benign, or reactive changes when rescreened, and 98% of these agreed with the original diagnosis. Sixteen percent of low-grade and 15% of high-grade intraepithelial lesions were classified as normal. The rank correlation between the rescreening scores and both proficiency tests was 0.24 using a scoring scheme for cytotechnologists. The correlation between the rescreening and proficiency testing scores indicates that performance on a 10-slide test gives some indication of the true performance of screeners. The computer-based test shows promise as an alternative to the glass slide test but needs further development and validation.

A biomechanical analysis of the orbitozygomatic complex in human cadavers: examination of load sharing and failure patterns following fixation with titanium and bioresorbable plating systems.

The orbitozygomatic complex (OZC) and zygomatic arch act as key buttresses in the restoration of midfacial projection and width in the treatment of panfacial fractures, yet little is known about the biomechanical and deformational forces placed on this region under applied load conditions. The aims of this project were (1) to study the stress-force relationships and load sharing of the intact human OZC under subfailure loads, (2) to assess load sharing and breaking strength of the OZC when intact and after four-point miniplate fixation with either titanium (1.2 and 1.7 mm) or bioresorbable (1.5 and 2.0 mm) systems, and (3) to analyze failure patterns. Using the MTS machine, fresh frozen human skulls stripped of soft tissue underwent loading with subfailure and failure forces directed in a standard fashion. Electrical resistance gauges applied directly to local and remote bony buttresses demonstrated temporary deformation at local (zygomatic arch, lateral and inferior orbital rim) and remote (supraorbital rim) buttresses under subfailure loading conditions. Breaking strength of the OZC (N = 10) measured before and after four-point application of 1.2- or 1.7-mm titanium or 1.5- or 2.0-mm bioresorbable miniplates demonstrated a significant (p < 0.05) decrease compared with intact controls. Surprisingly, the 2.0-mm bioresorbable miniplate construct provided only 13% of the intact breaking strength of the OZC compared with 39% for the 1.7-mm titanium system (p < 0.05). Plate bending or breakage was responsible for failure of the OZC following rigid fixation. Biomechanical testing of the OZC demonstrates (1) load sharing at regional and remote bony buttresses, (2) significant decreases in breaking strength following miniplate fixation, and (3) deformation of miniplates as a primary cause of failure under load conditions. Data generated from this project may be useful with regard to optimizing fixation of the OZC in the context and treatment of panfacial fractures.

Use of a polyglycolide lactide cement plug restrictor in total hip arthroplasty.

The use of a polyglycolide lactide cement plug restrictor in cemented femoral fixation during total hip arthroplasty was evaluated. Femoral cement pressurization was evaluated in vitro in a cadaveric model and the host response to polymer degradation was evaluated in vivo in a canine total hip arthroplasty model. Sixteen embalmed anatomic specimen femurs were prepared for cement femoral fixation. The intramedullary canal was plugged with either an ultrahigh molecular weight polyethylene cement plug restrictor or a polyglycolide lactide cement plug restrictor. Peak pressures in the proximal, mid, and distal portions of the cement mantle were recorded during cement insertion, cement pressurization, and implant insertion. There was no difference between the two plug groups in peak pressures throughout the cement mantle during cement insertion, pressurization, or implant insertion. Total hip arthroplasty using a cementless acetabular component and a cemented femoral stem was performed in 24 dogs. The femoral intramedullary canal was plugged with a polyethylene or a biodegradable cement plug restrictor. The dogs were sacrificed at 7 weeks, 10 months, or 15 months. Radiographically, no osteolytic lesions were seen around either plug type. Histomorphometrically, the polyglycolide lactide plugs appeared intact at 7 weeks and partially degraded by 10 and 15 months. In both plug groups, a mild fibrohistiocytic reaction with infiltration of fibrocytes, histocytes, and endothelial cells was seen. No osteolysis was observed. The results of the current study show that femoral cement pressurization can be attained in vitro using a biodegradable cement plug restrictor and that for as long as 15 months in the in vivo canine model there were no adverse reactions associated with use of these plugs compared with conventional ultrahigh molecular weight polyethylene plugs.