Inter-laboratory comparison of knee biomechanics and muscle activation patterns during gait in patients with knee osteoarthritis.

BACKGROUND: Gait analysis has been used for decades to quantify knee function in patients with knee osteoarthritis; however, it is unknown whether and to what extent inter-laboratory differences affect the comparison of gait data between studies. Therefore, the aim of this study was to perform an inter-laboratory comparison of knee biomechanics and muscle activation patterns during gait of patients with knee osteoarthritis. METHODS: Knee biomechanics and muscle activation patterns from patients with knee osteoarthritis were analyzed, previously collected at Dalhousie University (DAL: n = 55) and Amsterdam UMC, VU medical center (VUmc: n = 39), using their in-house protocols. Additionally, one healthy male was measured at both locations. Both direct comparisons and after harmonization of components of the protocols were made. Inter-laboratory comparisons were quantified using statistical parametric mapping analysis and discrete gait parameters. RESULTS: The inter-laboratory comparison showed offsets in the sagittal plane angles, moments and frontal plane angles, and phase shifts in the muscle activation patterns. Filter characteristics, initial contact identification and thigh anatomical frame definitions were harmonized between the laboratories. After this first step in protocol harmonization, the offsets in knee angles and sagittal plane moments remained, but the inter-laboratory comparison of the muscle activation patterns improved. CONCLUSIONS: Inter-laboratory differences obstruct valid comparisons of gait datasets from patients with knee osteoarthritis between gait laboratories. A first step in harmonization of gait analysis protocols improved the inter-laboratory comparison. Further protocol harmonization is recommended to enable valid comparisons between labs, data-sharing and multicenter trials to investigate knee function in patients with knee osteoarthritis.

Longitudinal dynamics of herd-level Mycobacterium bovis MLVA type surveillance in cattle in Northern Ireland 2003-2016.

Investigating genetically-structured diversity in pathogen populations over time is important to better understand disease maintenance and spread. Herd-level surveillance of Mycobacterium bovis genotypes (multi-locus VNTR analysis types, MLVA types) from all culture-confirmed bovine tuberculosis (TB) herd cases was undertaken in Northern Ireland (NI), generating an unparalleled, longitudinal, population-level 14-year survey for this pathogen. Across this population, 295 genetically-distinct M. bovis MLVA types were identified in the 19,717 M. bovis isolates surveyed. Of these, the most frequent was MLVA type 002 (23.0%); 151 MLVA types were represented more than once, in groups ranging from 2 to 4438 isolates. Only 23 MLVA types were isolated in all 14 years. Investigating inter-annual frequency of M. bovis MLVA types, examples of statistically-significant expansions (MLVA types 002, 004, 006, 009 and 027), contractions (MLVA types 001, 007 and 011) and maintenance (MLVA types 003 and 005) were disclosed, during a period of fluctuating bovine TB herd-level incidence at the NI scale. The fixed period frequency distribution of MLVA types remained highly right-skewed. Novel VNTR copy number variant MLVA types (N = 242; an average of 17 per annum) were identified throughout the survey. The MLVA type distribution in the landscape was not random; MLVA types showed statistically-significant geographical localization and strong spatial associations with Divisional Veterinary Office (DVO) regions. There was also evidence of differential risk of particular MLVA types across breeds (Holstein/Friesian vs. other), age-class, and sex and some evidence of an association between the number of animals testing positive for bovine TB during the disclosing test and particular MLVA types, although there was substantial variation.

Outcomes following excision of Morton's interdigital neuroma: a prospective study.

AIMS: This is the first prospective study to report the pre- and post-operative patient reported outcomes and satisfaction scores following excision of interdigital Morton's neuroma. PATIENTS AND METHODS: Between May 2006 and April 2013, we prospectively studied 99 consecutive patients (111 feet) who were to undergo excision of a Morton's neuroma. There were 78 women and 21 men with a mean age at the time of surgery of 56 years (22 to 78). Patients completed the Manchester-Oxford Foot Questionnaire (MOXFQ), Short Form-12 (SF-12) and a supplementary patient satisfaction survey three months pre-operatively and six months post-operatively. RESULTS: Statistically significant differences were found between the mean pre- and post-operative MOXFQ and the physical component of the SF-12 scores (p = 0.00081 and p = 0.00092 respectively). Most patients reported their overall satisfaction as excellent (n = 49, 49.5%) or good (n = 29, 29.3%), but ten patients were dissatisfied, reporting poor (n = 8, 8.1%) or very poor (n = 2, 2.0%) results. Only 63 patients (63%) were pain-free at follow-up: in eight patients (8.1%), the MOXFQ score worsened. There was no statistically significant difference in outcome between surgery on single or multiple sites. However, the MOXFQ scores were significantly worse after revision surgery (p = 0.004). CONCLUSIONS: The patient-reported outcomes after resection of a symptomatic Morton's neuroma are acceptable but may not be as good as earlier studies suggest. Surgery at several sites can be undertaken safely but caution should be exercised when considering revision surgery. Cite this article: Bone Joint J 2016;98-B:1376-81.

Knee effusion affects knee mechanics and muscle activity during gait in individuals with knee osteoarthritis.

OBJECTIVE: To test the hypothesis that knee effusion presence in those with knee osteoarthritis (OA) alters knee joint muscle activation patterns and sagittal plane mechanics during gait. METHODS: Thirty-five patients with medial compartment knee OA were assessed for the presence of effusion using a brush test. Based on the results, they were assigned to the knee effusion (n = 17) and no knee effusion (n = 18) groups. Electromyograms from seven lower extremity muscles (lateral and medial gastrocnemius, vastus lateralis and medialis, rectus femoris and the lateral and medial hamstrings), leg motion and ground reaction forces were recorded during self-selected walking. Isometric knee extensor, plantar flexor and knee flexor strength were measured. Discrete measures from angular knee motion and net external moment of force waveforms were identified. Principal component analysis extracted electromyographic waveform features. Analysis of variance models tested for main effects (group, muscle) and interactions (α = 0.05). Bonferroni post-hoc testing was employed. RESULTS: No differences in age, body mass index, knee pain, Western Ontario McMaster Osteoarthritis Index scores, gait velocity and muscle strength were found between groups (P > 0.05). Individuals with effusion had a greater overall quadriceps activation and prolonged hamstring activation into mid-stance (P < 0.05). Knee joint flexion angles were higher (P < 0.05) and net external knee extension (KE) moments in mid to late stance lower in the effusion group. CONCLUSION: Quadriceps and hamstrings activation during walking were altered when effusions were present. Increased knee flexion (KF) angles and decreased KE moment in mid-late stance provide a mechanical explanation for the effect of joint effusion on muscle activation in those with knee OA.

Physiological biomarkers of hypoxic stress in red swamp crayfish Procambarus clarkii from field and laboratory experiments.

The crayfish industry in Louisiana is the largest in the United States, with crayfish frequently harvested from waters that experience episodic or chronic hypoxia (dissolved oxygen [DO]≤ 2 mg/l). We examined physiological biomarkers (hemolymph lactate, glucose, and protein concentrations) of hypoxic stress in the red swamp crayfish Procambarus clarkii from chronically hypoxic natural habitats and laboratory hypoxia experiments. P. clarkii from normoxic and hypoxic areas in the Atchafalaya River Basin were sampled monthly from April to July 2010. Laboratory experiments subjected P. clarkii to severe hypoxia (1 mg/l DO), moderate hypoxia (2 mg/l DO), or normoxic conditions (control: DO>7.5 mg/l) for 12, 24, and 48 h. P. clarkii from normoxic and hypoxic natural habitats did not display significantly different hemolymph lactate or glucose concentrations; however, mean hemolymph protein concentration was significantly lower in crayfish from hypoxic areas. P. clarkii exposed to severe hypoxia in laboratory experiments had significantly higher hemolymph lactate and glucose concentrations for all three exposure times, whereas large differences in protein concentrations were not observed. These results suggest that elevated hemolymph lactate and glucose concentrations are responses to acute hypoxia in P. clarkii, while differences in protein concentrations are the result of chronic hypoxic exposure.

The neuromuscular demands of altering foot progression angle during gait in asymptomatic individuals and those with knee osteoarthritis.

OBJECTIVES: To determine the immediate effects of a toe-out foot progression angle modification during gait on the major lower limb muscle activation characteristics and to establish whether asymptomatic individuals and those with moderate knee OA have similar responses. DESIGN: Seventeen patients with knee OA and 20 asymptomatic control subjects participated. Informed consent was obtained. Electromyographic (EMG) recordings were acquired from the lateral and medial gastrocnemii, vastus lateralis, vastus medialis, rectus femoris and the lateral and medial hamstrings during neutral and toe-out walking conditions. The EMG waveforms were amplitude normalized to maximal voluntary isometric contractions and time normalized to the gait cycle. Principal component analysis extracted principal waveform features. Analysis of variance models tested for main effects and interactions. Bonferroni post hoc testing was employed (alpha=0.05). RESULTS: Both groups altered foot progression angle by approximately 15 degrees during toe-out walking (P<0.05). A shift in gastrocnemius activation towards later stance (P<0.05) and increased magnitude and duration of quadriceps activation (P<0.05) was found. A differential activation occurred in the overall magnitude and principal shape of the lateral and medial hamstring musculature in the asymptomatic group only (P<0.05). Significant group differences were shown in each muscle analysis (P<0.05). CONCLUSION: Neuromuscular demands of adopting a toe-out gait differ from a neutral foot progression angle. Demands also differ between asymptomatic controls and patients with moderate knee OA. These findings have relevance for altered joint loading and changes in metabolic cost of this gait modification in individuals with knee OA.

Foot progression angle and the knee adduction moment: a cross-sectional investigation in knee osteoarthritis.

OBJECTIVE: To test the hypothesis that an association exists between the characteristics of the knee adduction moment and foot progression angle (FPA) in asymptomatic individuals and those with mild to moderate and severe knee osteoarthritis (OA). DESIGN: Fifty asymptomatic individuals, 46 patients with mild to moderate and 44 patients with severe knee OA were recruited. Maximum knee adduction moment during late stance and principal component analysis (PCA) were used to describe the knee adduction moment captured during gait. Multiple regression models were used for each of the three group assignments to analyze the association between the independent variables and the knee adduction moment. RESULTS: FPA explained a significant amount of the variability associated with the shape of the knee adduction moment waveform for the asymptomatic and mild to moderate groups (P<0.05), but not for the severe group (P>0.05). Walking velocity alone explained significant variance associated with the shape of the knee adduction moment in the severe OA group (P<0.05). CONCLUSION: A toe out FPA was associated with altered knee adduction moment waveform characteristics, extracted using PCA, in asymptomatic individuals and those with mild to moderate knee OA only. These findings are directly implicated in medial knee compartment loading. This relationship was not evident in those with severe knee OA.

Surgical management and outcome of a type-III Salter-Harris fracture of the frontal plane of the distal radial physis in a foal.

CASE HISTORY: A 4-week-old Thoroughbred filly presented with lameness of acute, severe onset of the left foreleg (LF) of 3 days' duration. CLINICAL FINDINGS: Diffuse swelling was present around the distal radius and carpus of the LF. Carpal varus that could be reduced manually was present. Radiographs revealed an intra- articular frontal-plane fracture in the distal radial epiphysis, which continued cranially through the distal radial physis (DRP). The lateral aspect of the DRP was wider than expected. Latero-medial carpal instability was resolved by placement of a lag screw from the dorsal midline through the epiphysis across the fracture. The DRP closed prematurely, resulting in a non-reducible carpal varus deformity, which was partially corrected surgically, and reduced the length of the limb. DIAGNOSIS: Frontal-plane Salter-Harris type-III DRP fracture and varus deformity due to physeal injury. CLINICAL RELEVANCE: Frontal-plane Salter-Harris type- III fractures do not appear to have been previously reported in horses and may be associated with a poor prognosis for athletic activity.

Accuracy of dilution of morphine for intrathecal use.

Morphine is administered intrathecally alone or in combination with other drugs to provide spinal analgesia. Dose-finding studies have recommended 100 microg be used intrathecally to optimise analgesia and minimise side-effects for caesarean section and hip replacement surgery. Dilute solutions of morphine are generally not available, mandating preparation from a 10 mg/ml ampoule. We postulated that diluting morphine would be inaccurate and imprecise, contributing to the variability in patient response often reported. Twenty consultant and trainee anaesthetists were recruited and asked to prepare 100 microg of morphine from 10 mg/ml vials and from a hypothetical prediluted 500 microg/ml solution. The resultant samples were analysed using liquid chromatography. Prepared morphine doses ranged from 25 microg to 289 microg. Dilution of morphine was less accurate (P = 0.001) and more imprecise (P = 0.001) compared with using a prediluted solution. A single-step dilution technique using 0.1 ml of a solution diluted to 1.0 mg/ml was more accurate than when a double-dilution technique was used (P = 0.047). Given that dose-finding studies suggest that analgesia and side-effects vary at the dose range found in this study, we advocate the use of prediluted solutions. If dilution is to be performed a single-step dilution technique should be used.

Outcome of lag-screw treatment of incomplete fractures of the frontal plane of the radial facet of the third carpal bone in horses.

AIM: To describe outcomes for horses diagnosed with incomplete, non-displaced fractures of the frontal plane of the radial facet (INFR) of the third carpal bone (C3) treated by placement of a lag screw across the fracture under arthroscopic guidance. METHODS: Horses (n=13) diagnosed with INFR and treated between December 1999 and January 2005 using a lag screw placed over the fracture were studied. For each case, five horses matched for sire, age and sex which were not known to have INFR were sought for comparison. Racing performance data were collected from a commercial online database. The racing performance of cases pre- and post-operatively, and of cases and matched horses in the post-operative period was compared. RESULTS: Sixteen INFR were found in the 13 horses. Radiographic evidence of healed fracture lines 2-4 months after surgery was seen in 11/16 (69%) fractures; 11/13 (85%) cases raced again after a median recovery period of 292 (range 149-681) days. Treatment was considered successful in 9/13 (69%) cases, which were still in training or had been retired for reasons other than lameness localised to the middle carpal joint at the end of the study period. Just 6/13 (46%) cases had raced prior to injury. The racing ability pre- and post-operatively of five cases was compared, three (60%) of which performed better post-operatively than they had before. There was no significant difference in racing longevity or ability post-operatively between patients and matched (control) horses. CONCLUSIONS: Post-operatively, there was little difference in the racing performance between horses diagnosed with INFR which had a lag screw placed across the fracture line and horses matched for sire, age and sex which were not known to have INFR. CLINICAL RELEVANCE: Horses which were diagnosed with INFR of C3 and had a lag screw placed across the fracture had a good prognosis for future racing performance.

Tissue disposition, excretion and metabolism of 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) in male Sprague-Dawley rats.

The absorption, disposition, metabolism and excretion study of orally administered 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) was studied in conventional and bile-duct cannulated male rats. In conventional rats, >70% of the radiolabelled oral dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, gastrointestinal tract, skin, liver and lungs. Urinary excretion of BDE-100 was very low (0.1% of the dose). Biliary excretion of BDE-100 was slightly greater than that observed in urine, i.e. 1.7% at 72 h, and glucuronidation of phenolic metabolites was suggested. Thiol metabolites were not observed in the bile as had been reported in other PBDE metabolism studies. Almost 20% of the dose in conventional male rats and over 26% in bile-duct cannulated rats was excreted in the faeces, mainly as the unmetabolized parent, although large amounts of non-extractable radiolabel were also observed. Extractable metabolites in faeces were characterized by mass spectrometry. Monohydroxylated pentabromodiphenyl ether metabolites were detected; mono- and di-hydroxylated metabolites with accompanying oxidative debromination were also observed as faecal metabolites. Tissue residues of [(14)C]BDE-100 in liver, gastrointestinal tract and adipose tissue contained only parent material. The majority of the 0-72-h biliary radioactivity was associated with an unidentified 79-kDa protein or to albumin.

Environmental fate of roxarsone in poultry litter. I. Degradation of roxarsone during composting.

Roxarsone, 3-nitro-4-hydroxyphenylarsonic acid, is an organoarsenic compound that is used extensively in the feed of broiler poultry to control coccidial intestinal parasites, improve feed efficiency, and promote rapid growth. Nearly all the roxarsone in the feed is excreted unchanged in the manure. Poultry litter composed of the manure and bedding material has a high nutrient content and is used routinely as a fertilizer on cropland and pasture. Investigations were conducted to determine the fate of poultry-litter roxarsone in the environment Experiments indicated that roxarsone was stable in fresh dried litter; the primary arsenic species extracted with water from dried litter was roxarsone. However, when water was added to litter at about 50 wt % and the mixture was allowed to compost at 40 degrees C, the speciation of arsenic shifted from roxarsone to primarily arsenate in about 30 days. Increasing the amount of water increased the rate of degradation. Experiments also suggested that the degradation process most likely was biotic in nature. The rate of degradation was directly proportional to the incubation temperature; heat sterilization eliminated the degradation. Biotic degradation also was supported by results from enterobacteriaceae growth media that were inoculated with litter slurry to enhance the biotic processes and to reduce the concomitant abiotic effects from the complex litter solution. Samples collected from a variety of litter windrows in Arkansas, Oklahoma, and Maryland also showed that roxarsone originally present had been converted to arsenate.

Environmental fate of roxarsone in poultry litter. Part II. Mobility of arsenic in soils amended with poultry litter.

Poultry litter often contains arsenic as a result of organo-arsenical feed additives. When the poultry litter is applied to agricultural fields, the arsenic is released to the environment and may result in increased arsenic in surface and groundwater and increased uptake by plants. The release of arsenic from poultry litter, litter-amended soils, and soils without litter amendment was examined by extraction with water and strong acids (HCI and HNO3). The extracts were analyzed for As, C, P, Cu, Zn, and Fe. Copper, zinc, and iron are also poultry feed additives. Soils with a known history of litter application and controlled application rate of arsenic-containing poultry litter were obtained from the University of Maryland Agricultural Experiment Station. Soils from fields with long-term application of poultry litter were obtained from a tilled field on the Delmarva Peninsula (MD) and an untilled Oklahoma pasture. Samples from an adjacent forest or nearby pasture that had no history of litter application were used as controls. Depth profiles were sampled for the Oklahoma pasture soils. Analysis of the poultry litter showed that 75% of the arsenic was readily soluble in water. Extraction of soils shows that weakly bound arsenic mobilized by water correlates positively with C, P, Cu, and Zn in amended fields and appears to come primarily from the litter. Strongly bound arsenic correlates positively with Fe in amended fields and suggests sorption or coprecipitation of As and Fe in the soil column.

Photodegradation of roxarsone in poultry litter leachates.

Arsenic compounds have been used extensively in agriculture in the US for applications ranging from cotton herbicides to animal feed supplements. Roxarsone (3-nitro-4-hydroxyphenylarsonic acid), in particular, is used widely in poultry production to control coccidial intestinal parasites. It is excreted unchanged in the manure and introduced into the environment when litter is applied to farmland as fertilizer. Although the toxicity of roxarsone is less than that of inorganic arsenic, roxarsone can degrade, biotically and abiotically, to produce more toxic inorganic forms of arsenic, such as arsenite and arsenate. Experiments were conducted on aqueous litter leachates to test the stability of roxarsone under different conditions. Laboratory experiments have shown that arsenite can be cleaved photolytically from the roxarsone moiety at pH 4-8 and that the degradation rate increases with increasing pH. Furthermore, the rate of photodegradation increases with nitrate and natural organic matter concentration, reactants that are commonly found in poultry-litter-water leachates. Additional photochemical reactions rapidly oxidize the cleaved arsenite to arsenate. The formation of arsenate is not entirely undesirable, because it is less mobile in soil systems and less toxic than arsenite. A possible mechanism for the degradation of roxarsone in poultry litter leachates is proposed. The results suggest that poultry litter storage and field application practices could affect the degradation of roxarsone and subsequent mobilization of inorganic arsenic species.

Mass spectrometric identification of an azobenzene derivative produced by smectite-catalyzed conversion of 3-amino-4-hydroxyphenylarsonic acid.

The compound 3-amino-4-hydroxyphenylarsonic acid (3-amino-HPAA) reacts with smectite to form a soluble azobenzene arsonic acid compound. This reaction is of particular interest because it provides a possible mechanism for the formation of a new type of arsenic compound in natural water systems. 3-Amino-HPAA is a degradation product excreted by chickens that are fed rations amended with roxarsone. Roxarsone is used to control coccidial intestinal parasites in most of the broiler chickens grown in the United States. The structure of the azobenzene arsonic acid compound was first inferred from negative-ion and positive-ion low-resolution mass-spectrometric analyses of the supernatant of the smectite suspension. Elemental composition of the parent ion determined by high-resolution positive-ion mass spectrometric measurements was consistent with the proposed structure of the azobenzene arsonic acid compound.

Provision of laboratory services for heart and lung transplantation in Australia.

BACKGROUND: Laboratory services for the support of heart and lung transplantation in Australia have adapted to the special needs of the clinicians looking after the heart and lung transplantation patients. METHODS: Pre-transplantation standardized tests encompassing a wide variety of different parameters are carried out both to establish the suitability of patients for a transplant and to maximize the chance of success following this procedure. Potential solid organ recipients routinely have blood samples sent to a number of centers Australia-wide so that human leukocyte antigen (HLA) presensitization can be checked for at the time a donor becomes available in any state in Australia. Although prospective HLA matching is not performed for thoracic organ transplant recipients, pre-existing antibodies to donor HLA antigens are a contra-indication to transplantation. Following transplantation, the predominant roles of the laboratory are in the monitoring of immunosuppressive drug levels, in the detection of allograft rejection, and in the detection of bacterial infection or viral reactivation. While a number of markers have been proposed in the detection of rejection, we currently rely on interpretation of the histological analysis of biopsies. The treatment with immune suppressive agents, in particular cyclosporin A, has made organ transplantation from non-HLA identical donors possible. As cyclosporin A and other immune suppressive drugs have significant side effects, their concentrations need to be carefully followed to guarantee sufficient immune suppression while avoiding renal failure and other complications including excessive immunosuppression and infectious disease risk. Recently, the role of viral reactivation with the human cytomegalovirus (HCMV) has attained more prominence. HCMV is a potential pathogen in up to 90% of thoracic organ transplant recipients and in the pre-gancyclovir era, it was a major cause of morbidity and mortality in at-risk lung transplant recipients. New PCR-based assays that measure the viral load levels of HCMV allow earlier intervention and more appropriate treatment strategies to prevent the HCMV disease syndromes and optimize the HCMV prophylaxis strategy. CONCLUSIONS: Diagnostic pathology testing to support heart and lung transplantation is a combination of routine testing and specialized testing. Depending on the time-critical nature of the tests, this testing has to be done on site or in more centralized testing facilities. Further developments in the laboratory support of heart and lung transplantation will hopefully continue to improve both the short- and long-term outcomes of thoracic organ transplant recipients.

Treatment of plantar fasciitis.

Plantar fasciitis is a common cause of heel pain in adults. The disorder classically presents with pain that is particularly severe with the first few steps taken in the morning. In general, plantar fasciitis is a self-limited condition. However, symptoms usually resolve more quickly when the interval between the onset of symptoms and the onset of treatment is shorter. Many treatment options exist, including rest, stretching, strengthening, change of shoes, arch supports, orthotics, night splints, anti-inflammatory agents and surgery. Usually, plantar fasciitis can be treated successfully by tailoring treatment to an individual's risk factors and preferences.

Evaluation of microparticle enzyme immunoassay against HPLC-mass spectrometry for the determination of whole-blood tacrolimus in heart- and lung-transplant recipients.

OBJECTIVES: Tacrolimus is an immunosuppressant drug with a narrow therapeutic window and thus requires therapeutic drug monitoring. This study evaluates the suitability of the second-generation microparticle enzyme immunoassay (MEIA II) against a specific method, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS), for the measurement of tacrolimus in both heart- and lung-transplant groups. A secondary objective was to investigate the effect of tacrolimus concentration on MEIA II measurement. METHODS: The HPLC-MS assay was conducted as per our reported method and MEIA II performed according to manufacturer's instructions. Quality-control samples at 5, 11, and 22 microg/L were run in each batch to ensure assay integrity in both methods. Multiple trough samples from 18 heart patients (n = 126) and 17 lung patients (n = 203) were analyzed. RESULTS: The inter-batch imprecision and analytical recovery over the quality-control range by HPLC-MS (n = 12) was <6% and 98.2% to 104%, respectively, and by MEIA II (n = 16) <15% and 92.0% to 99.1%, respectively. The mean overestimation by MEIA II between the two methods for heart- and lung-transplant patient samples was found to be 9.9% (range: -37.4-45.4%) and 13.2% (range: -29.2-64.3%), respectively. Stratification of these data based on the tacrolimus concentration determined by MEIA II, yielded no statistically significant differences in bias between concentration subgroups within the clinically relevant range (p > 0.4). However, a statistically significant difference was detected between the highest concentration subgroup (>20.0 microg/L) and lower concentration subgroups in both transplant populations (p < 0.05). CONCLUSIONS: This study suggests that where HPLC-MS is not available, MEIA II may be suitable for the therapeutic drug monitoring of tacrolimus in heart- and lung-transplant recipients. However, the clinical importance of the observed mean bias, considering the wide range in overestimation in heart- and lung-transplant patient samples, is yet to be determined.

Pharmacokinetic assessment of oral ganciclovir in lung transplant recipients with cystic fibrosis.

Oral ganciclovir has been used as prophylaxis and therapy against cytomegalovirus in patients with HIV infection and following organ transplantation. Oral ganciclovir has clear practical advantages over intravenous ganciclovir but has a relatively low bioavailability and this may be problematic in at-risk patients with malabsorption. The bioavailability and therefore therapeutic potential of oral ganciclovir in cystic fibrosis (CF) patients post-lung transplant (LT) might be expected to be inadequate given the high incidence of malabsorption in these patients. An 8 h pharmacokinetic study was performed in 12 CF patients 160 +/- 122 days post-transplant who had been taking 1 g oral ganciclovir tds for 3 days with food (plus normal enzyme supplements). Mean (range) serum creatinine was 150 Imol/L (70-280). Blood was sampled at 0.5, 1, 2, 3, 4, 6 and 8 h post-final dose. Plasma was stored at -20 degrees C and later analysed by highperformance liquid chromatography. Mean peak concentration (C(max)) was 4.8 mg/L (0. 96-12.8), mean minimum concentration (C(min)) was 3.6 mg/L (0.78-11. 7) and mean area under the curve (AUC) was 35.4 mg.8 h/L (8-99). C(max), C(min) and AUC correlated significantly with one another (P < 0.001) as well as with serum creatinine and creatinine clearance (P < 0.01). When corrected for alterations in renal function, plasma oral ganciclovir levels are as predicted for other transplant populations. Three days of oral ganciclovir results in therapeutically useful plasma drug levels in the CF LT population, despite a background of general malabsorption. C(max), C(min) and AUC are highly correlated, allowing for the possibility of steady-state drug monitoring to confirm that the recommended dosing algorithm produces appropriate plasma levels.