Level of adherence to prescribed exercise in spondyloarthritis and factors affecting this adherence: a systematic review.

Adherence is a primary determinant of the effectiveness of any intervention. Exercise is considered essential in the management of spondyloarthritis (SpA); however, the overall adherence to exercise programmes and factors affecting adherence are unknown. The aim of this systematic review was to examine measures of, and factors influencing adherence to, prescribed exercise programmes in people with SpA. A search was performed in August 2018 using five data bases; the Cochrane library, CINAHL, EMBASE, MEDLINE, and Web of Science Collections. Inclusion criteria were: studies with adults (> 18 years) with SpA, with a prescribed exercise intervention or educational programme with the aim of increasing exercise participation. Article quality was independently assessed by two assessors. Extracted descriptive data included: populations, interventions, measures of adherence and factors affecting adherence. Percentage adherence rates to prescribed exercises were calculated if not reported. Nine studies were included with a total of 658 participants, 95% of participants had a diagnosis of ankylosing spondylitis. Interventions and measurement of adherence varied, making comparisons difficult. Rates of adherence ranged from 51.4 to 95%. Single studies identified; adherence improved following educational programmes, and higher disease severity and longer diagnostic delays were associated with higher adherence. Conflicting evidence was found as to whether supervision of exercise improved adherence. Three consecutive studies demonstrated adherence reduced over time. Adherence to prescribed exercise in SpA was poorly reported and predominately for people with AS. The levels of adherence and factors affecting prescribed exercise in SpA remain unclear. Future research should measure adherence across a longer time period and investigate possible factors which may influence adherence.

Ropivacaine plasma levels following high-dose local infiltration analgesia for total knee arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 28 patients aged 65 years or over undergoing unilateral total knee arthroplasty. Patients received infiltration of ropivacaine 400 mg followed by infusion at 20 mg.h(-1) through an intra-articular catheter. Total and free plasma levels of ropivacaine were measured at specified time intervals during a 24-h period after tourniquet release. Patients were monitored for symptoms and signs of local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.147 to 3.093 µg.ml(-1) (mean (SD) 1.105 (0.518) µg.ml(-1) ). Free levels of plasma ropivaca-ine varied from 0.001 to 0.104 µg.ml(-1) (mean (SD) 0.037 (0.020) µg.ml(-1) ). Six samples had total plasma ropivacaine levels greater the toxic threshold of 2.2 µg.ml(-1) . No samples reached the toxic threshold for free venous ropivacaine concentration. We conclude that the use of high-dose ropivacaine infiltration and catheter infusion for total knee arthroplasty in an elderly population does not result in free plasma ropivacaine levels previously associated with toxicity but that raised total plasma levels may be observed.

Ropivacaine plasma levels following local infiltration analgesia for primary total hip arthroplasty.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri-capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 µg.ml(-1) (mean (SD) 0.953 (0.323) µg.ml(-1) ). Free levels of plasma ropivacaine varied from 0.000 to 0.053 µg.ml(-1) (mean (SD) 0.024 (0.011) µg.ml(-1) ). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 µg.ml(-1) , free 0.15 µg.ml(-1) ) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients.

Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells.

We have investigated differences in gene expression between a metastatic and nonmetastatic clone of the DMBA-8 rat mammary adenocarcinoma cell line and have previously identified a differentially expressed gene WDNM1 (T.N. Dear, I.A. Ramshaw, and R.F. Kefford, Cancer Res., 48: 5203-5209, 1988). To further investigate differences in mRNA expression between these cell lines, a complementary DNA library from the nonmetastatic cell line was probed with labeled complementary DNA enriched for sequences specific to this line. We report here the identification in nonmetastatic cells of a second gene, WDNM2, which encodes a 1.7-kilobase mRNA corresponding to a protein (Mr 28,000-30,000) the expression of which shows a positive correlation with the nonmetastatic phenotype in three independently derived rat mammary adenocarcinoma cell lines and is regulated transcriptionally. Homologous sequences in the human genome have been identified. The function of this new gene may relate to regulation of the metastatic phenotype in this tumor.

The technique of delivery of peri-operative analgesia does not affect the rehabilitation or outcomes following total knee arthroplasty.

AIMS: This non-blinded randomised controlled trial compared the effect of patient-controlled epidural analgesia (PCEA) versus local infiltration analgesia (LIA) within an established enhanced recovery programme on the attainment of discharge criteria and recovery one year after total knee arthroplasty (TKA). The hypothesis was that LIA would increase the proportion of patients discharged from rehabilitation by the fourth post-operative day but would not affect outcomes at one year. PATIENTS AND METHODS: A total of 242 patients were randomised; 20 were excluded due to failure of spinal anaesthesia leaving 109 patients in the PCEA group and 113 in the LIA group. Patients were reviewed at six weeks and one year post-operatively. RESULTS: There was no difference in the proportion of patients discharged from rehabilitation by the fourth post-operative day, (77% in the PCEA group, 82% in the LIA group, p = 0.33), mean length of stay (four days in each group, p = 0.540), day of first mobilisation (p = 0.013) or pain (p = 0.278). There was no difference in mean Oxford Knee Scores (41 points in each group, p = 0.915) or the rate of complications in the two groups. CONCLUSION: Both techniques provided adequate pain relief, enabled early mobilisation and accelerated rehabilitation and good patient-reported outcomes up to one year post-operatively. PCEA and LIA are associated with similar clinical outcomes following TKA. Cite this article: Bone Joint J 2016;98-B1189-96.

Dehydroepiandrosterone sulfotransferase localization in human adrenal glands: a light and electron microscopic study.

Dehydroepiandrosterone sulfate is the major secretory product of the human adrenal cortex. The enzyme responsible for the sulfurylation, which has been isolated previously, possesses kinetic properties suggesting that it plays an important regulatory role in dehydroepiandrosterone sulfate secretion. In order to study the localization of the enzyme in the respective zones and cells of the cortex, an antibody to the pure enzyme was raised and the immunoglobulin G fraction employed in the peroxidase-antiperoxidase method. Staining was confined to the zona reticularis but was unevenly distributed throughout the cells. Electron microscopic examination of sections prepared from fresh adrenal tissue fixed in glutaraldehyde, revealed that the enzyme was predominantly clustered around lipid droplets. It is suggested that this may reflect an association of organelles, cholesterol being transported from lipid droplets to surrounding mitochondria, and pregnenolone then being converted to dehydroepiandrosterone in the adjacent endoplasmic reticulum and thence immediately sulfurylated.

Intranuclear post-transcriptional down-regulation responsible for loss of a keratin differentiation marker in tumour progression.

Apparent loss of differentiation markers characterizes advanced malignant neoplasms. Post-transcriptional down-regulation of keratin message to levels undetectable with a partial cDNA probe to rat keratin K5 had been observed in anaplastic cells (T952/F7) derived from benign keratin-producing cells (A5P/B10) (1). The entire fifth introns of both the K5 and K6 genes were generated from rat genomic DNA by PCR to define expression of these closely related proteins. Sequencing of the PCR products revealed 84% homology in the K5 and K6 exon regions included, but absence of any homology in the introns. Active transcription of K5 could be demonstrated in the anaplastic cells with reverse transcription of nuclear RNA (RTn-PCR) by the presence of PCR-generated products confirmed by sequencing as unspliced and spliced transcripts of rat K5. In situ hybridization with ssDNA probes for the spliced message from this region of the K5 gene demonstrated a punctuate distribution in the cytoplasm of the benign cells and absence of any detectable message in the anaplastic derivatives, ssDNA probes for the unspliced transcript containing intron 5 and the same flanking exon sequences as the spliced probe detected transcription of hnRNA in the anaplastic cells as discrete signals confined to the nuclear compartment. These results show that failure to express mRNA for a differentiation marker in the cytoplasm of anaplastic cells can be due to a mechanism operating in the nuclear compartment after gene transcription and indicate that the mechanism functions shortly after splicing of the transcript.

Isolation and preliminary characterisation of an X-ray-sensitive mammalian mutant cell line (WMXRS-1).

Mammalian cell lines that are sensitive to particular genotoxic agents have proved the most effective starting point for the cloning of human DNA-repair genes. After ethyl methanesulphonate mutagenesis of the parent murine fibroblast L-cell line, a new mammalian X-ray-sensitive cell line (WMXRS-1) was isolated. For selection of the mutant, a novel detection method was used: putative X-ray-sensitive clones were identified by their lack of incorporation of the DNA precursor, bromodeoxyuridine, after irradiation. The WMXRS-1 cell line was collaterally sensitive to ultraviolet radiation and some other agents known to be removed from DNA by the nucleotide excision repair pathway, but not to bleomycin or hydrogen peroxide. In relation to the wild-type strain, WMXRS-1 showed a similar pattern of induction of micronuclei up to an X-ray dose of 4 Gray and a similar DNA double-strand break (dsb) induction profile. The overall level of dsb rejoining was the same in the parent and mutant lines. However, WMXRS-1 demonstrated a reduced initial rate of dsb-rejoining, perhaps accounting for its radiosensitivity. WMXRS-1 also showed a greater G2 cell cycle phase accumulation after treatment with mitomycin-C. The cross-sensitivity profile and strand-break rejoining deficiency phenotype of WMXRS-1 is unique amongst previously characterised mammalian mutant cell lines.

Histiocytic necrotizing lymphadenitis (Kikuchi's disease): cytologic diagnosis by fine-needle biopsy.

A cytologic diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi's lymphadenitis) was made in a 14-yr-old female with cervical lymphadenopathy, fever, neutropenia, and hepatosplenomegaly. A predominance of reticulum cells, foamy macrophages, and karyorrhectic debris are clues to the diagnosis in the fine-needle biopsy smears. Subsequent histology confirmed the diagnosis of Kikuchi's lymphadenitis. The differential diagnoses are discussed including malignant lymphoma, which was excluded by morphology as well as flow cytometry and polymerase chain reaction (PCR) studies.

Lest the rhetoric begin: migration, population and the environment in Southern Africa.

In the spirited debate over cross-border migration in southern Africa there is one issue that has been conspicuously absent: the environment. The issue is raised in this article not because it necessarily deserves to be part of the debate--it will be argued, in fact that one needs to tread very carefully when drawing any linkages between migration and the environment--but because it has received an inordinate amount of attention in the academic and popular press in other parts of the world (particularly in the US) and could influence South African immigration policy and debates. In this article the authors look specifically at Thomas Homer-Dixon's influential work on environmental scarcity and migration and critically assess its relevance in the southern African context. A brief review of the history of migration and immigration policy in the region is followed by a theoretical and empirical critique of Homer Dixon's writings. It is acknowledged in the article that environmental degradation can (and does) contribute to forced migration and violent conflict in southern Africa, but it is also argued that Homer-Dixon misses some fundamental points about the political economy of (post) apartheid southern Africa and in doing so presents a very problematic interpretation of the causes and effects of migration in the region. The potential for these theories to lend themselves to a reactionary, closed-border approach to immigration in South Africa is also discussed and forms part of the impetus for the writing of this paper.

An anatomic study of local infiltration analgesia in total knee arthroplasty.

BACKGROUND: Local infiltration analgesia (LIA) is a relatively novel technique developed for effective pain control following total knee arthroplasty (TKA), reducing requirements for epidural or parenteral postoperative analgesia. This study investigated the anatomical spread of an LIA used in TKA to identify the nerve structures reached by the injected fluid. METHODS: Six fresh-frozen cadaveric lower limbs were injected according to a standardised LIA technique with a solution of latex and India ink to enable visualisation. Wounds were closed and limbs placed flat in a freezer at -20°C for two weeks. Limbs were then either sliced or dissected to identify solution locations. RESULTS: Solution was found from the proximal thigh to the middle of the lower leg. The main areas of concentration were the popliteal fossa, the anterior aspect of the femur and the subcutaneous tissue of the anterior aspect of the knee. There was less solution in the lower popliteal fossa. The solution was found to reach the majority of nerves, with good infiltration of nerves supplying the knee. CONCLUSIONS: These results support the positive clinical outcomes with this LIA technique. However, the lack of infiltration into the lower popliteal fossa suggests more fluid or a different injection point could be used. The solution reaching the extensor muscles of the lower leg is likely to have no beneficial analgesic effect for a TKA patient. The LIA technique is already used in clinical practice following total knee arthroplasty. Results from this study show there may be scope to optimise the injection sites in LIA technique.

An enhanced recovery programme for primary total knee arthroplasty in the United Kingdom--follow up at one year.

The concepts of Enhanced Recovery Programmes (ERP) are to reduce peri-operative morbidity whilst accelerating patient's rehabilitation resulting in a shortened hospital stay following primary joint arthroplasty. These programmes should include all patients undergoing surgery and should not be selective. We report a consecutive series of 1081 primary total knee arthroplasties undergoing an enhanced recovery programme with a one year follow up period. A comparative cohort of 735 patients from immediately prior to the enhanced recovery programme implementation was also reviewed. The median day of discharge home was reduced from post-operative day six to day four (p<0.001) for the ERP group. Post-operative urinary catheterisation (35% vs. 6.9%) and blood transfusion (3.7% vs. 0.6%) rates were significantly reduced (p<0.001). Within the ERP group median pain scores (0 = no pain, 10 = maximal pain) on mobilisation were three throughout hospital stay with 95% of patients ambulating within 24h. No statistical difference was found in post-operative thrombolytic events (p=0.35 and 0.5), infection (p=0.86), mortality rates (p=0.8) and Oxford Knee Scores (p=0.99) at follow up. This multidisciplinary approach provided satisfactory post-operative analgesia allowing early safe ambulation and expedited discharge to home with no detriment to continuing rehabilitation, infection or complication rates at one year.

Reliability, validity and utility of the Fitness Interview Test.

Psychiatrists are being asked more and more often by the courts to determine whether or not criminal defendants are fit to stand trial. However, the Criminal Code provides few statutory guidelines on what constitutes fitness to stand trial. Perhaps as a result of the lack of standards, psychiatrists have typically relied on traditional clinical assessment procedures in determining whether or not an individual is fit to stand trial. In an effort to improve the quality and consistency of forensic assessments, researchers have designed instruments to assess fitness to stand trial. In Canada, the Fitness Interview Test (FIT) was developed for this purpose. This study evaluated the FIT for its validity, reliability and utility in the assessment of fitness. The FIT was found to have excellent interrater reliability and scale homogeneity. In addition, it was able to discriminate between groups of defendants rates as being fit and or unfit to stand trial. The scale did not seem to be differentially sensitive to the diverse facets of fitness, which may be attributed to the format and content of the scale items. Caution is advised in the use of the FIT pending revision of the scale.

Post-transcriptional regulation of urokinase plasminogen activator gene expression occurs in the nucleus of BC1 rat mammary tumor cells.

The regulation of urokinase plasminogen activator (uPA) expression was investigated in 2 highly metastatic rat mammary adenocarcinoma cell lines, BC1 and MAT 13762. BC1 cells were observed to synthesize, on average, 10 times less uPA enzyme and mRNA than MAT 13762 cells; however this difference was not accounted for by differences in uPA gene copy number/structure or in the rate of uPA gene transcription in the cell lines studied. Moreover, Northern blot analysis of invasive sub-populations derived in vitro from the BC1 cell line revealed levels of uPA expression similar to those of the parent, but a 3-fold elevation in expression of the metalloprotease gene, transin. Further investigation showed that treatment of BC1 cells with either of the protein synthesis inhibitors, cycloheximide or anisomycin, increased the level of both nuclear and cytoplasmic uPA RNA 6- to 18-fold in 4 hr, whilst inducing a maximum 2.6-fold increase in the rate of uPA gene transcription. This increase in uPA gene expression may therefore reflect, in part, an increase in the stability and/or processing of nuclear uPA transcripts. These results suggest that the degree of uPA gene expression does not correlate directly with BC1 tumor-cell invasion in vitro, and that the uPA gene is down-regulated, at least in part, post-transcriptionally in the nucleus of BC1 mammary tumor cells.

Use of Fourier series for the analysis of biological systems.

In an attempt to quantitate the physical behavior of biological systems, Fourier analysis has been applied to the respiratory and circulatory systems by a number of investigators. The validity of this application has been questioned on the basis that these systems are nonlinear and not strictly periodic. If these objections were valid much of the more recent work in this field would have to be re-evaluated. The applicability of Fourier analysis to these two systems was therefore investigated, both theoretically and experimentally, using on-line analysis on a LINC (laboratory instrument computer) digital computer. In normal anesthetized dogs errors introduced by deviations from periodicity and linearity were found to be within the range of measurement errors. In sinusoidally perfused aortas the amount of second harmonic produced by the vessel was less than 5%. In addition, the magnitude of errors due to faulty determination of cycle length, sampling techniques, aliasing, and A-D (analogue to digital) conversion were evaluated and found to be within the noise level of the measuring equipment when appropriate techniques were employed. Utmost care has to be used in the coupling between a transducer and the system to be measured, and dynamic calibration before each experiment is a prerequisite for successful analysis. With presently available equipment the static measurement errors can be reduced to +/-0.2 cm H(2)O for pressure transducers, 0.1 cm(3)/sec for electromagnetic flowmeters, and 5 x 10(-4) cm for measurement of radius changes. The frequency response of this equipment once properly coupled to the system is flat to at least 20 cycle/sec.

Use of archival and fresh cytologic material for the polymerase chain reaction. Detection of the bcl-2 oncogene in lymphoid tissue obtained by fine needle biopsy.

A technique for extracting DNA from archival and fresh tissue from fine needle biopsy (FNB) samples for the polymerase chain reaction (PCR) is described. The method was used to detect the bcl-2 oncogene in various cytologic lymphoid preparations. The DNA was amplified with primers specific for the major break point region of the t(14;18) translocation, and the presence of the bcl-2 oncogene was correlated with clinical, cytomorphologic, histologic and immunologic findings. Thirty patients who had FNB of lymphoid tissue were randomly selected, 18 retrospectively and 12 prospectively. Bcl-2 was present in 3 of 8 cases of reactive lymphadenopathy and 9 of 22 cases of non-Hodgkin's lymphoma. Of these, seven had follicular small cleaved cell lymphoma, and two had large cell lymphoma. Smears, both archival and fresh, and cell suspensions provided sufficient DNA for PCR amplification. The technique has potential applications in several areas of cytologic and hematologic practice.