Axial rotation and pain are associated with facet joint osteoarthritis in adolescent idiopathic scoliosis.

OBJECTIVE: Facet joints are crucial for spinal stability but develop premature osteoarthritis in patients with adolescent idiopathic scoliosis (AIS). Here, we evaluated the association between facet joint cartilage and subchondral bone homeostasis, perceived back pain and 3-dimensional spinal deformity to better understand the role of facet joint degeneration in AIS progression and pain. METHOD: The osteoarthritic state of cartilage and bone of AIS facet joint surgical samples were characterized using histological OARSI scoring, visual morphological grading and µCT analysis, respectively. Back pain was self-reported using a numerical rating scale and expressed relative to the location on the patient's back. The scoliotic curves from our patient cohort were digitally reconstructed using biplanar radiographs and the eOS system (EOS imaging). The deformity was then reduced to three intervertebral angles (coronal, sagittal and axial) for each pair of bilateral facet joints. Statistical associations between the intervertebral angles, osteoarthritis parameters and pain intensity were performed using the Spearman method and Friedman test. RESULTS: Facet joint cartilage degeneration was associated with decreased subchondral bone volume and quality. Most importantly, asymmetrical, and overall degeneration of facet joints was strongly correlated to intervertebral axial rotation. Additionally, kyphotic intervertebral segments in the sagittal plane were good predictors of increased facet joint degeneration and back pain. CONCLUSION: Facet joint degeneration is associated with axial deformity, kyphotic intervertebral angle and back pain intensity in AIS. These results suggest that facet joints are important features to consider for rotational instability in AIS spines and related disease progression and perceived back pain.

For whom the disc tolls: intervertebral disc degeneration, back pain and toll-like receptors.

Intervertebral disc (IVD) degeneration is characterised by catabolic and inflammatory processes that contribute largely to tissue degradation and chronic back pain. The disc cells are responsible for the pathological production of pro-inflammatory cytokines and catabolic enzymes leading to degeneration. However, this phenotypical change is poorly understood. Growing evidence in animal and human studies implicates Toll-like receptors (TLR) and their activation through danger-associated alarmins, found increasingly in degenerating IVDs. TLR signalling results in the release of pro-inflammatory cytokines and proteolytic enzymes that can directly cause IVD degeneration and back pain. This review aims to summarise the current literature on TLR activation in IVD degeneration and discuss potential treatment modalities to alleviate the inflammatory phenotype of disc cells in order to arrest IVD degeneration and back pain.

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications.

Autologous NP cell implantation is a potential therapeutic avenue for intervertebral disc (IVD) degeneration. However, monolayer expansion of cells isolated from surgical samples may negatively impact matrix production by way of dedifferentiation. Previously, we have used a continuous expansion culture system to successfully preserve a chondrocyte phenotype. In this work, we hypothesised that continuous expansion culture could also preserve nucleus pulposus (NP) phenotype. We confirmed that serial passaging drove NP dedifferentiation by significantly decreasing collagen type II, aggrecan and chondroadherin (CHAD) gene expression, compared to freshly isolated cells. Proliferation, gene expression profile and matrix production in both culture conditions were compared using primary bovine NP cells. Both standard culture and continuous culture produced clinically relevant cell populations. However, continuous culture cells maintained significantly higher collagen type II, aggrecan and CHAD transcript expression levels. Also, continuous expansion cells generated greater amounts of proteoglycan, collagen type II and aggrecan protein deposition in pellet cultures. To our surprise, continuous expansion of human intervertebral disc cells - isolated from acute herniation tissue - produced less collagen type II, aggrecan and CHAD genes and proteins, compared to standard culture. Also, continuous culture of cells isolated from young non-degenerate tissue did not preserve gene and protein expression, compared to standard culture. These data indicated that primary bovine and human NP cells responded differently to continuous culture, where the positive effects observed for bovine cells did not translate to human cells. Therefore, caution must be exercised when choosing animal models and cell sources for pre-clinical studies.

A simple tool to measure patient perceptions of operative birth.

OBJECTIVE: To assess the feasibility and validity of a maternal satisfaction measurement tool, the SaFE study Patient Perception Score (PPS), after operative delivery. DESIGN: Cross-sectional survey. SETTING: A large maternity unit in England. SAMPLE: 150 women who had had an operative birth. METHODS: We recruited women within 24 hours of birth and quantified their satisfaction with two questionnaires: PPS, and the Mackey Childbirth Satisfaction Rating Scale (CSRS; modified). MAIN OUTCOME MEASURES: Participation rate to determine feasibility; Cronbach's alpha as measure of internal consistency; PPS satisfaction scores for groups of accoucheurs of different seniority to assess construct validity; correlation coefficient of PPS scores with total scores from the CSRS questionnaire to establish criterion validity. RESULTS: Participation rate approached 85%. We observed high scores for most births except a few outliers. Internal consistency of the PPS was high (Cronbach's alpha=0.83). Total PPS scores correlated strongly with total CSRS scores (Spearman's r=0.64, P<0.001). CONCLUSIONS: The PPS is a simple and valid tool for patient-centred assessments. High scores were observed for most births but there were a small minority of accoucheurs who consistently scored poorly and these data could be used during appraisal and training.

Value and face validity of objective structured assessment of technical skills (OSATS) for work based assessment of surgical skills in obstetrics and gynaecology.

BACKGROUND: Changes in UK Junior Doctor working patterns, reduced training hours and increased patient expectations have resulted in less exposure of Juniors to surgical procedures. Validated methods of assessment are therefore required to assure the surgical competency of future Consultants. Objective Structured Assessment of Technical Skills (OSATS) forms are one possible tool. AIMS: To investigate trainee and trainer perceptions of the value and validity of OSATS in the operating theatre. METHOD: OSATS forms and feedback questionnaires. RESULTS: 38 trainees and 16 trainers provided feedback on the OSATS forms used during 60 procedures, returning 119 questionnaires in total. Value : 85% of trainee and 76% of trainer responses agreed/strongly agreed that OSATS would improve trainees' surgical skills. Face validity: 80% of trainee and 76% of trainer responses agreed/strongly agreed with OSATS ability to assess surgical skills. APPLICATION: 76% of trainee and trainer responses agreed/strongly agreed that OSATS should become part of the annual assessment process for trainees. CONCLUSIONS: Trainees and trainers perceive OSATS to be a valuable and valid tool for the objective assessment of surgical skills in the work place. More research is required to assess their criterion-related, content, construct and predictive validity as well as their reliability in the workplace.

Amenorrhoea despite displaced levonorgestrel intra-uterine system.

PIP: A 29-year-old woman presented to the gynecology outpatient clinic with abdominal discomfort following the insertion of a levonorgestrel intrauterine system (LNG-IUS). It was noted that although the patient remained amenorrheic since the insertion, there was a persistent left iliac fossa discomfort, which was constant in nature and not made worse by intercourse. On examination, there was a vague tenderness in the left iliac fossa, and a transvaginal ultrasound scan showed bright echoes outside the uterus suggestive of an extrauterine IUS. Thus, arrangements were made for an admission for hysteroscopy and laparoscopy, proceeding to laparotomy if required. Following the procedures, the patient reported disappearance of the discomfort, although the LNG-IUS had not yet been retrieved. X-ray revealed the device lying high in the abdomen and laparoscopy was conducted. The LNG-IUS itself was buried, but was easily retrieved with gentle counteraction on the omentum through a 5 mm laparoscopy portal. Overall, this case emphasizes the importance of an X-ray as well as an ultrasound investigation in such cases.^ieng

Human sexuality in long-term care.

Sexual expression is a basic human need, a normal part of life that is integral to who we are as human beings. As we age, we continue to be challenged to grow in every area of our lives, including our sexuality. In institutionalized settings, however, human sexuality can be an area in which growth is not fostered, but restrained. Challenges leading to restraint include limited privacy, concerns about the consent of cognitively impaired sexual partners and conflicts with the personal values of institutional staff. Challenges exist in many areas, including inappropriate sexual expression toward a staff member or other residents.

Effect of head-out water immersion on serum sodium transport inhibitor and urinary nonadrenaline excretion in pre-menopausal women.

The effect of head out water immersion on the excretion of catecholamines and serum sodium transport inhibitor (STI) was studied in healthy young women during the follicular and leuteal phases. Two way ANOVA showed that menstrual cycle had no effect on the excretion of noradrenaline (NA), dopamine (DA) or serum STI. Analysis of pooled data from follicular and leuteal phases showed that immersion caused a significant increase in sodium excretion and serum STI and a significant decrease in urinary NA excretion in healthy young women. After immersion, sodium excretion, DA excretion and serum STI decreased and NA increased.

Antigen-induced alveolitis: cytokine production in a mouse model.

Mice of the C57BL/6 strain were injected intraperitoneally with 10(8) sheep red blood cells (SRBC), then instilled intratracheally with 10(8) SRBC two to three weeks later. After a single intratracheal exposure, a significant cellular infiltrate occurred, composed mostly of macrophages and lymphocytes. Lymphocytes proliferated significantly in response to SRBC antigen in vitro and released interleukin-2 (IL-2). Alveolar macrophages isolated from mice challenged with SRBC released higher levels of IL-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) upon in vitro lipopolysaccharide (LPS) stimulation compared to unprimed, challenged mice or mice receiving intraperitoneal SRBC alone. Lymphocytes from primed mice challenged three times with SRBC proliferated significantly less in response to the antigen than mice receiving one SRBC challenge and released significant levels of interferon gamma (IFN-gamma). Bronchoalveolar macrophages isolated from primed mice given three SRBC challenges released slightly higher levels of TNF-alpha and IL-6 in response to LPS than those from unprimed mice. After the third instillation, levels of hydroxyproline in the lungs increased significantly, indicative of a fibrotic reaction. Neutralization of IL-1 (by anti-mouse type 1 IL-1 receptor) or TNF-alpha resulted in the partial abrogation of the initial neutrophil influx, with some effect on the subsequent lymphocyte and macrophage influx. Blocking IL-1 or IL-2 but not TNF-alpha also resulted in a significant decrease in lung hydroxyproline increase, as well as lung granulomatous response and fibrosis. Overall, these results suggest that lymphoproliferation in the lungs in response to an antigen can result in fibrosis, mediated in part by IL-2 and IL-1.

Blockade of leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation.

We examined the contribution of the leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation determined by exposure to the thermophilic actinomycete Faeni rectivirgula. The exposure generated a large influx of cells in the bronchoalveolar space and in the lung parenchyma, as seen from enhanced numbers of cells recovered by bronchoalveolar lavage (BAL) and histologic scoring of lung lesions. Repeated intranasal exposure to F. rectivirgula also resulted in a significant increase in lung hydroxyproline levels. Histologic analysis showed that alveolar wall inflammation, interstitial swelling and congestion, epithelial cell destruction, and granulomas with occasional epithelioid cells were observed in the lungs of challenged mice. Mice injected with rat antibodies against LFA-1 concomitantly with an antigen challenge showed no reduction in the number of BAL inflammatory cells, but lung fibrosis was significantly reduced by anti-LFA-1 treatment as assessed by lung hydroxyproline levels; parenchymal inflammation and tissue damage were also significantly reduced as seen from morphometric analysis. Anti-LFA-1 treatment of mice with established hypersensitivity pneumonitis was found to significantly reduce the levels of lung hydroxyproline and tissue damage; the numbers of BAL cells remained unaffected. From these results, we conclude that the fibrosis and tissue-damaging reactions in hypersensitivity pneumonitis, but not the alveolitis, are partly dependent on LFA-1-mediated cellular interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular and cytokine profiles in spontaneous regression phase of hypersensitivity pneumonitis.

The phase of spontaneous regression of hypersensitivity pneumonitis was evaluated using a mouse model. C57BL/6 mice were instilled intranasally with 150 micrograms of the thermophilic actinomycete Faeni rectivirgula 3 days a week so as to establish a mouse model of farmer's lungs. It was shown that instillation of mice for a period of more than 6 weeks was associated with a significant decrease in the lung inflammation, suggestive of the so-called spontaneous regression phase seen in this pathology. Indeed, the lung index was seen to decrease after more than 6 weeks of treatment (2.2 after 6 weeks vs. 1.7 at 12 weeks, p < .01). There was also a significant decrease in lung hydroxyproline levels in animals given 12 weeks of treatment (175 micrograms/lung) compared to 6-week-treated animals (212 micrograms/lung, p < .05). Treated mice did not show a significant decrease in the alveolitis after 9 weeks of treatment. Also, there was no evidence that there was a decrease in bronchoalveolar lavage macrophage or T lymphocyte activity in mice given more than 9 weeks of F. rectivirgula treatment, as judged by O2- release and antigen-driven proliferation. Conversely, it was shown that NK cell activity in the lung digest of mice given 9 to 12 weeks of instillation was significantly higher than that seen in mice given 6 weeks of treatment. Analysis of the lung cell cytokine profile seen after ConA mitogenesis showed that after 6 weeks of F. rectivirgula treatments, nonparenchymal cells secreted high levels of tumor necrosis factor alpha (TNF alpha) and granulocyte macrophage colony-stimulating-factor (GM-CSF), whereas similar cells from the lungs of mice given 9-12 weeks of treatment secreted larger amounts of interferon-gamma (IFN gamma) and interleukin-2 (IL-2). Overall, these results suggest that the spontaneous regression phase is associated with changes in NK cell activity and lung cell lymphokine profile.

Renal sodium retention does not occur during the luteal phase of the menstrual cycle in normal women.

OBJECTIVE: To determine whether weight gain due to renal sodium and water retention occurs in the luteal phase of the normal menstrual cycle. DESIGN: Prospective observational study. SETTING: Research laboratory installed with modified spa bath. SUBJECTS: Ten normal healthy women. INTERVENTION: Each subject underwent two experiments, one in each phase of the menstrual cycle, involving 3 h head-out water immersion and a pre- and post immersion control hour. 25 ml blood samples were obtained every hour before, during and after water immersion. MAIN OUTCOME MEASURES: Renal and hormonal responses to water immersion during the luteal and proliferative phases of the cycle. RESULTS: There was no change in weight, creatinine clearance, basal sodium excretion or plasma atrial natriuretic peptide between the two phases of the cycle. There was a significant rise in basal progesterone, plasma aldosterone and plasma renin activity in the luteal phase of the ovulatory cycles. Renal and hormonal responses to immersion including sodium and calcium excretion, elevation of atrial natriuretic peptide (ANP) and suppression of plasma aldosterone and plasma renin activity were identical in the two phases of the menstrual cycle. CONCLUSION: We found no evidence to support the hypothesis that renal sodium and water retention occurs in the luteal phase of the normal menstrual cycle.

Assessment and management of hypertensive disorders in pregnancy by health professionals in the Avon district.

A questionnaire based survey was carried out in the Avon health districts to investigate the assessment and management of hypertensive disorders in the third trimester of pregnancy by health professionals. A total of 673 responses were analysed from 310 general practitioners, 48 hospital doctors, 214 hospital midwives, 81 community midwives and 120 student midwives. The study revealed a wide variation in the criteria used for the diagnosis of a hypertensive disorder in pregnancy and some outmoded recommendations for management. The importance of continuing education is stressed, in order to ensure that current research and the consensus of expert opinion is being relayed to the personnel involved in antenatal care.

Mobility of polychlorinated aromatic compounds in soils contaminated with wood-preserving oil.

Greater understanding of the mobility of polychlorinated aromatic compounds in soils is needed to investigate contamination and design suitable remediation strategies for sites contaminated with wood-preserving oil. The objectives of this study were (1) to develop a suitable aqueous batch extraction method for soil containing wood-preservative residues; (2) to determine partition coefficients for the primary contaminants [pentachlorophenol (PCP), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFS)] in oil, soil, and aqueous phases; and (3) to evaluate the potential soil migration of the primary contaminants. In a three-phase oil-soil-water mixture, PCP, PCDDs, and PCDFs were partitioned to the greatest extent in the oil phase. These results suggest that the migration of contaminants can occur in a saturated subsurface soil zone containing an oil phase at a wood-preserving site. In the absence of a free oil phase, PCDDs and PCDFs were highly partitioned onto soil and were considered non-leachable in the aqueous phase. However, PCP was considered highly leachable from contaminated soil containing only an aqueous liquid phase. Results from this study indicate that removal of any free oil phase present in subsurface soil should have highest priority during the cleanup of contaminated wood-preserving sites.

Quartz exposure, retention, and early silicosis in sheep.

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.