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Biomedical subjects

P J Richards

Publications and source records attributed to P J Richards.

At least 19 recordsLinked to original sources

Assessment of CAOS as a training model in spinal surgery: a randomised study.

The objectives of this study were (1) to quantify the benefit of computer assisted orthopaedic surgery (CAOS) pedicle screw insertion in a porcine cadaver model evaluated by dissection and computed tomography (CT); (2) to compare the effect on performance of four surgeons with no experience of CAOS, and varying experience of pedicle screw insertion; (3) to see if CT with extended windows was an acceptable method to evaluate the position of the pedicle screws in the porcine cadaver model, compared to dissection. This was a prospective, randomised, controlled and blinded porcine cadaver study. Twelve 6-month-old porcine (white skinned Landrace) lumbar spines were scanned pre-operatively by spiral CT, as required for the CAOS computer data set. Computer randomisation allocated the specimens to one of four surgeons, all new to CAOS but with different levels of experience in spinal surgery. The usual anatomical landmarks for the freehand technique were known to all four surgeons. Two pedicles at each vertebral level were randomly allocated between conventional free hand insertion and an electromagnetic image guided surgery (NAVITRAK) and 6.5 mm cancellous AO screws inserted. Post-operatively, spiral CT was blindly evaluated by an independent radiologist and the spine fellow to assess the accuracy of pedicle screw placement, by each method. The inter- and intra-observer reliability of CT was evaluated compared to dissection. The pedicle screw placement was assessed as perfect if within the pedicle along its central axis, or acceptable (within < 2 mm from perfect), and measured in millimetres from perfect thereafter. One hundred and sixty-six of 168 pedicles in 12 porcine spines were operated on. Complete data were present for 163 pedicles (81 CAOS, 82 freehand). In the CAOS group 84% of screws were deemed acceptable or perfect, compared to 75.6% with the freehand technique. Screw misplacement was significantly reduced using CAOS (P = 0.049). Seventy-nine percent of CAOS screws were ideally placed compared with 64% with a conventional freehand technique (P = 0.05). A logistic linear regression model showed that the miss placed pedicle screw rate was significantly reduced using CAOS (P = 0.047). CAOS benefited the least experienced surgeons most (the research registrars acceptable rate increased from 70 to 90% and the spine fellow from 76 to 86%). CAOS did not have a statistically significant effect on the experienced consultant spine surgeon increasing from 70 to 79% (P = 0.39). The experienced general orthopaedic surgeon did not benefit from CAOS (P = 0.5). CT compared to dissection showed an intra-observer reliability of 99.4% and inter-observer reliability of 92.6%. The conclusions of this study were as follows: (1) an increased number of pedicle screws were ideally placed using the CAOS electromagnetic guidance system compared to the conventional freehand technique; (2) junior surgeons benefited most from CAOS; (3) we believe CAOS (Navitrak) with porcine lumbar spines evaluated by post operative CT, represents a useful model for training junior surgeons in pedicle screw placement; (4) experienced spine surgeons, who have never used CAOS, may find CAOS less helpful than previously reported.

Animals↗

The distribution of microvascular response in Achilles tendonopathy assessed by colour and power Doppler.

OBJECTIVES: To assess the distribution of microvascular response on colour Doppler (CD) and power Doppler (PD) ultrasound (US) of the tendo Achilles (TA) in tendonopathy, and to look for any relationship between tendon morphology and symptoms. DESIGN AND PATIENTS: A retrospective, observational study was carried out on consecutive ambulant US patients with suspected tendonopathy, presenting with pain or an Achilles mass. Exclusion criteria were: use of steroids, and previous or possible rupture or surgery in either tendon or arthropathy. Using a 5-12 MHz linear array probe (ATL HDI 3000) both TAs were scanned. Tendonopathy was defined as tendon swelling and/or hypoechogenicity of the TA. The site, number and distribution of microvascularity, on CD and PD, and the anteroposterior size were recorded, with the analysis masked. RESULTS: Fifty-two patients presented with TA pain and six also with swelling. There were 34 males and 18 females, aged from 11 to 78 years (mean 45 years). Fifty-five TAs that showed tendonopathy with hypoechogenic areas were all observed to be over 5.9 mm (mean 11.1 mm, range 5.9-20 mm), of which 45 were symptomatic with abnormal PD and 24 with abnormal CD flow. It was observed that the extent and completeness of vessel branching was more extensive on PD than CD. All TAs demonstrating tendonopathy were over 5.9 mm in adults and all TAs that showed PD flow were over 6.5 mm. All microvessels originated towards the TA from the ventral surface usually into tendonopathy, and were 16-fold more frequent around the margins. There were 49 TAs with normal spectral US, and with no PD flow, with a mean size of 4.5 mm (range 3.0-7.4 mm). For the right and left TAs independently analysed and taking the 40 patients with a paired asymptomatic and symptomatic tendon: (1) There was a highly significant difference in size (P<0.00001) using the paired t-test (parametric) between the asymptomatic tendon (mean 5.2+/-1.4 mm (1 SD)), and the contralateral morphologically abnormal and symptomatic side (mean 9.7+/-1.4 mm). (2) There was no linear Pearson correlation (0.25) between TA size and duration of symptoms (P=0.11) for symptomatic tendons. (3) There was a positive Spearman correlation (0.84) between the number of vessels and TA size (P<0.00001). (4) There was a significant difference in the number of PD vessels using the non-parametric Wilcoxon signed test (P<0.00001) between the symptomatic and asymptomatic groups. CONCLUSIONS: (1) PD shows more tendon microvascularity than CD in TA tendonopathy. (2) All microvessels arise on the ventral side of the TA. (3) There is a non-linear relationship between tendonopathy, TA size and the amount of microvascularity, but not between PD and duration of symptoms. (4) Morphologically abnormal adult TAs were larger than 5.9 mm, and PD flow was only seen in TAs above 6.5 mm.

Achilles Tendon↗

Deletion of the gene encoding CD59a in mice increases disease severity in a murine model of rheumatoid arthritis.

OBJECTIVE: To investigate the roles of CD59a in the protection of joint tissue in the context of murine antigen-induced arthritis (AIA). METHODS: AIA was triggered in CD59a-deficient (CD59a(-/-)) mice and in CD59a-sufficient (CD59a(+/+)) controls; the course and severity of disease were compared between groups. The effects on arthritis of restoring CD59 to the joint in CD59a(-/-) mice by use of a membrane-targeted recombinant CD59 were also explored. RESULTS: Disease, as assessed clinically by measurement of joint swelling on day 1 (P < 0.0001), day 2 (P < 0.01), and day 7 (P < 0.02) and histologically from indicators of joint damage on day 21 (P < 0.02), was significantly enhanced in CD59a(-/-) mice compared with CD59a(+/+) wild-type controls. Membrane attack complex (MAC) deposition in the arthritic joints of CD59a(-/-) mice was also increased compared with that in the joints of CD59a(+/+) controls. Restitution of CD59 activity in joints of CD59a(-/-) mice was attempted with soluble recombinant rat CD59 (sCD59) or with a novel membrane-targeted rat CD59 derivative (sCD59-APT542). Strong immunohistochemical staining of the synovial membrane and subsynovial tissue was apparent in sCD59-APT542-injected joints, but not in joints injected with untargeted sCD59. Intraarticular administration of sCD59-APT542 markedly ameliorated disease severity in CD59a(-/-) mice, knee swelling was significantly reduced over the time course of the disease, and joint damage, assessed histologically, was significantly milder on day 21 (P < 0.05). CONCLUSION: These data firmly implicate the MAC of complement as a major effector of joint damage in the murine AIA model of rheumatoid arthritis (RA), and they provide a rationale for the inhibition of MAC assembly as a therapeutic strategy for RA.

Adjuvants, Immunologic↗

The emergency department: an appropriate referral rate for radiography.

AIM: To evaluate the hypothesis that where there is good clinical practice in an emergency department (ED), there is a low uptake of plain radiography. MATERIALS AND METHODS: Emergency notes and radiography records were reviewed over one week in January 1999, to determine the rate of radiography of first time attenders at the North Staffordshire NHS Trust. The clinical appropriateness of the imaging was assessed by pairs of radiology specialist registrars and casualty physicians. They judged the appropriateness of the imaging by the 1998 Royal College of Radiologists (RCR) guidelines and/or their clinical judgement, by consensus. Where there was no consensus or the data appeared incomplete, the radiology and ED consultant reviewed the notes. RESULTS: A total of 1615 notes were found out of 1643 (98%). Of these, 147 (9%) return attenders were excluded and 32 patients left without being seen. The number of first time attenders was 1436 (87%), of whom 637 (44%) were radiographed; 95% of these radiography examinations were appropriate and 5% were inappropriate. Of the first time attenders who were not radiographed the decision was appropriate in 95% of cases, and inappropriate for 5%, i.e. 5% of those who had no radiography, should have been X-rayed. There were no disagreements between RCR guidelines and the clinical judgements, but in 16% there were no suitable RCR guidelines. Junior doctors were not always able to find the relevant RCR guideline (relevant clinical guideline found in 73% of cases) in the guideline book, compared to the consultants (relevant clinical guideline found in 84% of cases). CONCLUSION: The application of the RCR guidelines is taken as representing good clinical practice in determining when to refer a patient for radiography. Based on this assumption, a referral rate for radiography of 44% of first time attenders was found to be appropriate. This referral rate can be taken as a benchmark. A benchmark is necessary in order to allow departments to make a local assessment as to whether their local referral rate is likely to be too high or too low.

Clinical Competence↗

Review of the radiology in randomised controlled trials in open reduction and internal fixation (ORIF) of displaced intraarticular calcaneal fractures.

The aim of this study was to assess the radiological evaluation of all prospective, randomised, controlled trails of displaced intraarticular calcaneal fractures. A systematic review of the literature, of which only three of 296 references were randomised and controlled, were examined in a blinded fashion. All had preoperative coronal CT for Sander's classification and used a lateral surgical approach or conservative treatment. Thordason (15 patients/11 controls) used interoperative lateral and axial X-rays. Bohler's angle increased on average from 11 to 26 degrees (P<0.001) postoperatively, but decreased (9-8 degrees ) in the conservative group. The posterior facet residual displacement was 1.1 and 4.7 mm, respectively. O'Farrell (12 patients/12 controls) showed 8 out of 12 had Bohler's and Gissane's angle partially or fully restored postoperatively, and not conservatively. Parmar (25 patients/31 controls) used preoperative lateral radiographs, but failed with CT to grade the postoperative reduction, whilst the conservative group was unaltered. There was no systematic, blinded assessment of the change in radiology by the operative intervention. Overall there was weak evidence to support ORIF. In conclusion, there are only three randomised, controlled studies involving small numbers of patients, which showed improved plain radiographic anatomical alignment, in the postoperative but not conservative group. Further prospective randomised, controlled trials with independent and blinded assessment with accurate CT and clinical evaluation will be required before ORIF can be adopted as the best practice.

Calcaneus↗

Achilles tendon (TA) size and power Doppler ultrasound (PD) changes compared to MRI: a preliminary observational study.

AIM: To assess whether abnormal Achilles tendon (TA) magnetic resonance imaging (MRI) and spectral ultrasound (US) features have associated development of microvascular power Doppler (PD) flow. MATERIALS AND METHODS: In a prospective, controlled and blinded study six patients with TA symptoms were compared to five with other ankle abnormalities. Two radiologists independently measured the mean maximal anteroposterior diameter on MRI and conventional US (categorized as normal <6 mm, mild 6.1-10 mm, moderate 1.1-1.5 cm and severely enlarged > 1.6 cm), assessed morphology and studied the vessels using power Doppler. They formed a consensus over discrepancies. Sonography of the contralateral side within 24 h was used as a control. RESULTS: Twenty-one tendons in six women and five men, aged 45-77 years (mean 57.6 years), were examined, 12 tendons were of normal US morphology and size (< 6 mm), and did not exhibit PD's flow (interobserver agreement K > 0.74). Of the 12 tendons studied by MRI five were normal, seven tendons were enlarged, five of which had a proportionate increase in PD flow at the margin on the deep surface and four also had vessels in the centre of the tendon. All five of these tendons had high signal on T2-weighting (T2W). Of the two mildly enlarged tendons of intermediate signal on T1 and T2W, one showed PD flow and the other did not. CONCLUSIONS: In patients with TA disease power Doppler ultrasound shows proliferation of vessels in enlarged, abnormal tendons demonstrated on MRI and standard ultrasound, in the absence of definite tears.

Achilles Tendon↗

Amelioration of rat antigen-induced arthritis by liposomally conjugated methotrexate is accompanied by down-regulation of cytokine mRNA expression.

OBJECTIVES: We examined the temporal changes in the expression of interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV). METHODS: On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and TNF-alpha) using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. CONCLUSIONS: Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1beta and IL-6 inhibition.

Animals↗

Suppression of chronic streptococcal cell wall-induced arthritis in Lewis rats by liposomal clodronate.

OBJECTIVES: To investigate the role of macrophages in the pathogenesis of chronic streptococcal cell wall (SCW)-induced arthritis using liposomal clodronate. METHODS: Female Lewis rats with SCW-induced arthritis received a single intravenous injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) 10 days post-arthritis induction. RESULTS: SUVc significantly suppressed the development of chronic SCW-induced arthritis for up to 26 days after treatment. At this time point, ED1(+) macrophages were significantly depleted in the liver and ankle joints, although splenic macrophage numbers were not significantly different from control groups. Macrophage elimination induced a significant reduction in local levels of interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha) and matrix metalloproteinase-9 (MMP-9) from ankle joints. CONCLUSIONS: Macrophage elimination by SUVc inhibits local production of IL-1beta, IL-6, TNFalpha and MMP-9, and the pathogenesis of inflammatory arthritis.

Animals↗

Interventions for treating calcaneal fractures.

BACKGROUND: Fracture of the calcaneus (os calcis or heel bone) comprises one to two per cent of all fractures. OBJECTIVES: To identify and evaluate randomised trials of treatments for calcaneal fractures. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, the Cochrane Controlled Trials Register, and the Cochrane Musculoskeletal Injuries Group Trials Register were searched. We checked reference lists of relevant articles and contacted trialists and experts in the field. Date of the most recent search: October 1998. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing interventions for treating patients with calcaneal fractures. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, using a 12 item scale, and extracted data. Wherever appropriate and possible, results were pooled. MAIN RESULTS: Of the six relevant randomised trials identified, four were included, one excluded and one is ongoing. All four included trials had methodological flaws. Three trials, involving 134 patients, compared open reduction and internal fixation with non-operative management of displaced intra-articular fractures. Pooled results showed no apparent difference in residual pain (24/40 versus 24/42; Peto odds ratio 0.90, 95% confidence interval 0.34 to 2.36), but a lower proportion of the operative group was unable to return to the same work (11/45 versus 23/45; Peto odds ratio 0.30, 95% confidence interval 0.13 to 0.71), and was unable to wear the same shoes as before (12/52 versus 24/54; Peto odds ratio 0.37, 95% confidence interval 0.17 to 0.84). One trial, involving 23 patients, evaluated impulse compression therapy. At one year there was a mean difference of 1.40 pain units on a visual analogue score (scale 0-10) (95% confidence interval 0.02 to 2.82) in favour of the treated group. The impulse compression group had greater subtalar movement (mean difference 14.0 degrees, 95% confidence interval 3.2 to 24.6) at three months. On average, patients in the impulse compression group returned to work three months earlier than those in the control group. REVIEWER'S CONCLUSIONS: Randomised trials of management of calcaneal fractures are few, small and generally of poor quality. Even where there is some evidence of benefit of operative compared with non-operative treatment, it remains unclear whether the possible advantages of surgery are worth its risks. Given this it seems best to wait for the results of one large ongoing trial on open reduction and internal fixation against conservative treatment. One very small trial suggests that impulse compression therapy for intra-articular calcaneal fractures may be beneficial. More large-scale, high quality randomised controlled trials are needed to confirm these results, and to test other interventions in the treatment of calcaneal fractures.

Calcaneus↗

Pro-inflammatory effects of the aminobisphosphonate ibandronate in vitro and in vivo.

OBJECTIVES: To investigate the effects of the aminobisphosphonate, ibandronate, on the course of joint inflammation in rat antigen-induced arthritis (AIA) and the release of pro-inflammatory cytokines in partially purified human peripheral blood mononuclear cells (PBMC). METHODS: Rats with AIA received a single intra-articular injection of ibandronate (1 mg) 7 days post-arthritis induction and knee swelling was measured for 7 days thereafter. The effects of ibandronate (300 microg/ml) on PBMC cytokine production and activation marker expression were determined using polymerase chain reaction (PCR)/ELISA and FACS analysis, respectively. RESULTS: Joint swelling, associated with AIA, was sustained in ibandronate-treated rats compared with saline-treated control rats. Ibandronate stimulated the production of interferon gamma (IFN-gamma) in adherent PBMC, and increased the surface expression of FcgammaRI and HLA DP, DQ, DR on the adherent monocyte population. Activation by lipopolysaccharide (LPS) of PBMC previously incubated with ibandronate led to enhanced levels of tumour necrosis factor alpha (TNF-alpha) secretion, and this could be partially inhibited by neutralizing antibodies to IFN-gamma. CONCLUSIONS: The enhanced production of TNF-alpha by ibandronate-treated PBMC in vitro involves stimulation of adherent monocytes by IFN-gamma prior to LPS-induced activation. Similar cellular interactions may be involved in the pro-inflammatory effects of ibandronate in vivo.

Animals↗

Liposomal clodronate eliminates synovial macrophages, reduces inflammation and ameliorates joint destruction in antigen-induced arthritis.

OBJECTIVES: To investigate the efficacy of a single i.v. dose of clodronate encapsulated within small unilamellar vesicles in suppressing joint inflammation and the histological progression of rat antigen-induced arthritis (AIA). METHODS: Rats with AIA received a single i.v. injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) or larger multilamellar vesicles (MLVc) 7 days post-arthritis induction. Free clodronate or saline were used as negative controls. RESULTS: SUVc was shown to be more effective than MLVc, sustaining a significant reduction in knee swelling for up to 7 days after the initial systemic administration. Knee swelling in free clodronate-treated animals was not significantly affected. The increased efficacy of SUVc in reducing inflammation and joint destruction was associated with a significant depletion of resident ED1+, ED2+ and ED3+ macrophages from the synovial membrane (SM). CONCLUSIONS: SUVc is more efficient than MLVc in reducing the severity of inflammation and joint destruction in rat AIA, and is associated with the specific elimination of macrophage subpopulations from the SM.

Analgesics, Non-Narcotic↗

Avoiding drunk drivers: the level and sources of protective behavior.

Drunk driving has been a concern for a decade and a half, with most discussions of its control centering on offenders. Research on the extent to which citizens engage in behaviors to avoid becoming victims of drunk drivers, however, is in short supply. This project examines the level of participation in protective behaviors, and it assesses the potential sources of self- and other-protection. Our findings indicate that substantial proportions of citizens take action to protect themselves and others from victimization by drunk drivers. We also find limited support for the fear/victimization model and no support for a collective security explanation of protective behavior.

Accidents, Traffic↗

Chest imaging in AIDS.

A review of imaging in the acquired immune deficiency syndrome (AIDS) is presented. The imaging features can be conveniently categorized according to whether the presenting complications are infective (bacterial, protozoal, or fungal), bronchiectasis, neoplastic (Kaposi's sarcoma, AIDS-related lymphoma, or lymphoproliferative disease), or a miscellaneous group (non-specific interstitial pneumonitis, persistent generalized lymphadenopathy, or bronchogenic carcinoma).

AIDS-Related Opportunistic Infections↗

High resolution computed tomography in HIV patients with suspected Pneumocystis carinii pneumonia and a normal chest radiograph.

AIM: To correlate the appearances of high resolution computed tomography (HRCT) with the bronchoalveolar lavage (BAL) findings in HIV positive patients in whom there is a strong clinical suspicion of Pneumocystis carinii pneumonia (PCP) but a normal chest radiograph. PATIENTS AND METHODS: The 13 patients available for analysis fulfilled the following criteria: HIV positive, CD4 count less than 200 cells per mm3, non-productive cough or non-purulent sputum daily, documented fever above 37.5 degrees C for more than a week, dyspnoea or decreased exercise tolerance and normal chest X-ray. HRCT of the lungs was performed within 24 h of the chest radiograph, using 1 mm slice at 2 cm intervals, reconstructed using a high resolution algorithm. Bronchoalveolar lavage samples were taken for cytological examination, microscopy, culture and sensitivity. The HCRT findings were correlated with the results of BAL and clinical outcome. RESULTS: Of the 13 patients studied, four had patchy ground-glass opacities and one also had interstitial thickening. All four proved to have PCP on BAL. None of the nine patients who were negative for PCP on BAL had ground-glass opacity or abnormalities attributable to PCP. CONCLUSION: In this study HRCT showed abnormalities consistent with PCP in all four patients who had PCP on BAL before there were chest radiograph abnormalities. The use of HRCT may help avoid unnecessary delay, allow early medical intervention and, if our results are confirmed by larger series, may reduce the need for bronchoscopy.

AIDS-Related Opportunistic Infections↗