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Biomedical subjects

E McNally

Publications and source records attributed to E McNally.

At least 19 recordsLinked to original sources

Evaluation of patellar tracking in symptomatic and asymptomatic individuals by magnetic resonance imaging.

OBJECTIVE: To determine the patterns of patellar motion in subjects without knee symptoms using dynamic magnetic resonance imaging (MRI). DESIGN: Patellar tracking MR examinations were performed on 50 asymptomatic volunteers. The presence and degree of lateral subluxation and tilt of the patella was assessed independently by three radiologists, and discrepancies resolved by consensus. Using the same criteria, the tracking pattern in 50 consecutive patients, recently referred for imaging assessment of anterior knee pain, was studied. PATIENTS: Fifty volunteers (22 male, mean age 37 years) and 50 unmatched patients (15 male, mean age 25.5 years) were examined. RESULTS AND CONCLUSIONS: Forty-one per cent of a total of 97 knees in the volunteer group showed evidence of lateral subluxation, which was either minimal (grade 1, 32%) or minor (grade 2, 9%). No volunteer demonstrated major (grade 3) subluxation; lateral tilt without translation of the patella was also seen (2%). In the patient group, higher grades of lateral subluxation were more common. Minimal (grade 1) lateralization is a common movement pattern of the patella on knee extension, and should be regarded as normal.

Adolescent↗

Heterotopic bone formation following hip arthroplasty in Paget's disease.

Heterotopic bone formation in soft tissues occurs commonly in Paget's disease patients following a primary total hip arthroplasty (THA). The nature of this heterotopic bone has not been documented. In this report, we show that the heterotopic bone removed 14 years after primary THA in a case of Paget's disease was sclerotic, contained prominent mosaic cement lines and showed increased remodelling activity on the bone surface. In addition to these typically Pagetic histological features, it was noted ultrastructurally that the osteoclasts contained characteristic intranuclear viral-like inclusions. In contrast, the foreign body macrophages found in the joint pseudocapsule and pseudomembrane, which are a population of mononuclear precursor cells from which osteoclasts can be formed, did not contain viral-like inclusions. These findings are of interest regarding the pathogenesis of heterotopic bone formation following hip arthroplasty and the ontogeny of Pagetic osteoclasts.

Aged↗

Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.

OBJECTIVE: To determine the frequency and clinical predictors of sacroiliitis diagnosed by magnetic resonance imaging (MRI) in a psoriatic arthritis (PsA) population. METHODS: The studied comprised 103 patients with PsA. A careful clinical assessment for sacroiliitis was made from history and examination, and HLA-B27 testing was performed. Sixty-eight patients underwent tilted coronal fat-saturated T1-weighted and STIR MRI of the sacroiliac joints. RESULTS: Clinical features of moderate or severe sacroiliitis were found in 24/68 (35%) patients. MRI features of sacroiliitis were found in 26/68 (38%) patients. Clinical features of sacroiliitis were present in 14/42 (33%) with normal MRI scans and 10/26 (38%) with abnormal scans (normal vs abnormal scans, P = 0.7). The presence of sacroiliitis on MRI was associated with restricted spinal movements (P = 0.004) and the duration of PsA (P = 0.04). There was no correlation between HLA-B27 and sacroiliitis diagnosed by MRI. CONCLUSION: Sacroiliitis diagnosed by MRI occurs commonly in PsA but is difficult to detect clinically.

Adult↗

Mutations in the caveolin-3 gene: When are they pathogenic?

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic disorders usually with autosomal recessive (AR) inheritance and, less often, displaying autosomal dominant (AD) inheritance. Mutations in the caveolin-3 gene (CAV-3) associated with a reduction of protein expression cause AD-LGMD1C muscular dystrophy. Based on a previous study in the American and Brazilian population, it has been suggested that CAV-3 mutations might also cause AR-LGMD. Here we report the analysis of the CAV-3 gene in 61 additional Brazilian LGMD patients and 100 additional Brazilian normal controls. Two rare G55S and C71W missense changes previously detected only in LGMD patients (and not detected in 100 normal controls from the American population) were now found in normal Brazilian controls. In addition, we have identified a novel R125H missense change in one LGMD female patient that was also found in two of her unaffected siblings. These observations, together with the normal immunofluorescence caveolin pattern in the muscle biopsy from two patients with the G55W and R125H changes in the CAV-3 gene suggest that the G55S, C71W, and R125H polymorphisms, on their own, are not sufficient to produce the pathology.

Adult↗

Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial.

CONTEXT: Attachment of most rhinovirus subtypes to cells depends on a cellular receptor, the intercellular adhesion molecule 1 (ICAM-1). A recombinant soluble ICAM-1 (tremacamra, formerly BIRR 4) has shown possible efficacy in early studies. OBJECTIVE: To determine the efficacy and safety of intranasal administration of tremacamra in experimental rhinovirus colds in humans. DESIGN: Four randomized, double-blind, placebo-controlled trials conducted in January to March 1996. SETTING AND SUBJECTS: Volunteers between the ages of 18 and 60 years who had an antibody titer of 1:4 or less to the challenge virus. Subjects were isolated in a hotel room during study days 0 to 8; symptoms were recorded through day 14. A total of 198 subjects were randomized, of whom 196 received drug or placebo and were included in the safety analysis. A total of 177 subjects were included in the efficacy analysis. INTERVENTIONS: Tremacamra or placebo was given beginning 7 hours before inoculation with rhinovirus type 39 (preinoculation studies) or 12 hours after (postinoculation studies). Tremacamra as an inhaled solution or as a powder (each given preinoculation and postinoculation for a total of 4 studies) and placebo were given in 6 doses at 3-hour intervals daily during days 1 through 7. Recipients of active treatment received 367 microg of tremacamra per nostril per dose for a total of 4.4 mg/d. MAIN OUTCOME MEASURES: Effect of tremacamra on infection, as determined by virus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study interaction was not significant, so results were pooled for the main analysis. RESULTS: A total of 88 (92%) of the 96 subjects in the placebo groups and 69 (85%) of the 81 subjects in the active treatment groups were infected (P=.19). For placebo vs tremacamra, respectively, the total symptom score (+/- 95% confidence interval [CI]) was 17.6 (+/- 2.7) vs 9.6 (+/- 2.9), the proportion of clinical colds was 64/96 (67% +/- 9%) vs 36/81 (44% +/- 11%), and the nasal mucus weight was 32.9 (+/- 8.8) g vs 14.5 (+/- 9.4) g (P<.001 for all comparisons). Tremacamra was not associated with adverse effects or evidence of absorption through the nasal mucosa and did not interfere with development of neutralizing antibody. CONCLUSION: Tremacamra reduced the severity of experimental rhinovirus colds. Whether tremacamra will be useful clinically will require further study.

Administration, Intranasal↗

The role of MRI in the diagnosis of occult hip fractures.

Undisplaced fractures of the hip can occasionally be difficult to diagnose on radiographs. We performed MRI scans on 33 patients who had post-traumatic painful hips but negative radiographs. Forty per cent of the patients had sustained a fractured neck of femur, 15 per cent had sustained an intertrochanteric fracture and 11 per cent had sustained other fractures around the hip; in one patient a tumour was demonstrated. No fracture was seen in 30 per cent of the patients scanned. MRI is well tolerated by elderly patients in pain, does not involve ionising radiation and provides early and accurate diagnosis in patients with X-ray negative post-traumatic hip pain.

Accidental Falls↗

The effect on patients of non-referral for skull radiography following mild head injury.

This paper assesses the attitude of 705 patients who attended the Accident department of a large metropolitan district general hospital, with a mild head injury and who were not referred for skull radiography. A questionnaire was sent to patients 5-7 months after they had attended. Fifty-one per cent had expected an X-ray, and when this did not occur, the majority of this group (63 per cent) left the Accident department disappointed. Furthermore, the duration of symptoms in this group was prolonged. The introduction of guidelines may reduce clinically unnecessary X-ray examinations, but some of the consequences may not be fully appreciated. In this study, a significant number of patients were dissatisfied with the lack of X-ray referral. The main cause for the associated prolongation of symptoms is not clear, but a contributory factory may be that lack of referral for radiography led to anxiety concerning the thoroughness of their management.

Attitude to Health↗

Use of ionising radiation by professional football clubs to assess asymptomatic transfer candidates.

The financial considerations of transfer candidates in the football league is such that a detailed medical examination as well as other investigations are required prior to a successful transfer. With this in mind the concern is raised that professional footballers may be exposed to excessive ionising radiation by undergoing unnecessary radiological imaging. Our study was conducted in order to assess the use of plain films in the assessment of transfer candidates in the premier league

Arthrography↗

The native structure of intercellular adhesion molecule-1 (ICAM-1) is a dimer. Correlation with binding to LFA-1.

In solution, intercellular adhesion molecule-1 (ICAM-1) exhibits extremely low affinity for its receptor, LFA-1, as direct binding to LFA-1 has not been reported. Furthermore, there are conflicting reports on the ability of ICAM-1 in solution to inhibit cell adhesion events. These differences could be due to the valency or an oligomeric native biochemical form of membrane-bound and soluble ICAM-1, which may correlate with its ability to bind to integrins. To test this, stimulated adenocarcinoma (A549) cells or HUVEC were labeled with 35S-methionine/cysteine and treated with a chemical cross-linker. A high m.w. form (200 kDa) of ICAM-1 but not ICAM-2 was specifically immunoprecipitated from cross-linked cell lysates and supernatants. Affinity purification of crosslinked supernatants revealed that the majority of ICAM-1 was dimeric as opposed to recombinant soluble ICAM-1, which contains a minor fraction of dimer. Gel filtration chromatography was used to isolate monomeric and dimer-rich fractions of recombinant soluble ICAM-1, and tested for direct binding to affinity-purified LFA-1. Dimer-rich fractions demonstrated an enhanced ability and estimated affinity, compared with monomeric protein, to bind to purified LFA-1. These data suggest that ICAM-1 exists in its native membrane-bound and shed form as a non-covalent dimer, and that dimerization directly correlates with enhanced binding to LFA-1.

Cross-Linking Reagents↗

Posters for accident departments: simple method of sustaining reduction in x ray examinations.

OBJECTIVE: To assess whether a simple strategy would sustain a reduction in the number of unnecessary x ray examinations. DESIGN: Use of posters to display guidelines encouraging the more effective use of radiology in patients with head injuries, twisted ankles, neck injuries, and abdominal pain. SETTING: Accident department of a large metropolitan district general hospital. PATIENTS: 15,875 patients attending the accident department over two years. MAIN OUTCOME MEASURE: Proportion of patients having radiography. RESULTS: Referrals for skull radiography fell from 56% to 20% and those for abdominal radiography fell from 31% to 7%. Referral patterns for adults attending with twisted ankles and cervical spine injuries did not change. Reductions were sustained over two years. CONCLUSION: Carefully designed posters provide a simple method of reducing unnecessary x ray examinations.

Audiovisual Aids↗

Primary adhalin deficiency as a cause of muscular dystrophy in patients with normal dystrophin.

In our experience, more than half of muscular dystrophy patients show a primary dystrophinopathy. The underlying cause of muscular dystrophy in the vast majority of patients with normal dystrophin is unknown. Recently, a French family with 4 young siblings showing a muscular dystrophy of unknown progression was shown to have a primary deficiency of "adhalin," the 50-kd dystrophin-associated protein. Here we report the screening of the entire adhalin coding sequence in muscle biopsy specimens from 30 muscular dystrophy patients to (1) determine whether adhalin deficiency is restricted to the French population, (2) determine the incidence of adhalin deficiency in muscular dystrophy patients, and (3) characterize the clinical features and mutations in adhalin-deficient patients. We identified a single African-American girl with childhood-onset muscular dystrophy and adhalin gene mutations. We found her to be a compound heterozygote for two different mutations of the same amino acid (Arg98Cys; Arg98His), one of which was previously identified in the French family. Our results suggest that primary adhalin deficiency in patients with muscular dystrophy but normal dystrophin is relatively infrequent, and that adhalin-deficient patients are not restricted to the French population.

Adolescent↗

Technical note: identifying and aspirating hip effusions.

Ultrasound has become a routine investigation in the investigation of the painful hip in children. It has been recommended that all effusions demonstrated by sonography be drained. Based on the experience of 800 hip aspirations, the authors describe an approach to the demonstration and aspiration of hip effusions with some of the pitfalls that result in false positive and false negative diagnoses.

Adolescent↗

Reversible hypercapnia in acute exacerbations of chronic obstructive pulmonary disease (COPD).

We prospectively studied emergency hospitalizations due to acute exacerbations of chronic obstructive pulmonary disease (COPD) among 74 hypercapnic patients, in order to determine factors which predict reversal to normocapnia as a result of therapy. Clinical, arterial blood gas and pulmonary function data on presentation were compared to predischarge values among those 58 patients who survived the admission. Patients were divided into those who reverted to normocapnia (reversible, 40% of surviving patients), and those who remained hypercapnic (chronic, 60% of surviving patients). Reversible patients had higher admission arterial oxygen tension (PaO2) levels than those with chronic hypercapnia (6.4 +/- 1.3 kPa (mean +/- SD), as compared to 5.7 +/- 1.1 kPa) better pulmonary function (forced expiratory volume in one second (FEV1) 35 +/- 16% predicted, as compared to 26 +/- 7.9), and a lower prevalence of cor pulmonale (30% as compared to 63% of patients). No admission variable(s) distinguished individual patients as reversible or chronic hypercapnic, and, in particular, admission arterial carbon dioxide tension (PaCO2) and pH levels were similar in both groups. Furthermore, there were no differences between survivors and those 16 patients who died during the admission, apart from a higher urea level among those who died. These findings suggest that reversible patients have milder underlying disease than those with chronic hypercapnia. Our data establish the high prevalence of reversible hypercapnia among patients hospitalized with exacerbations of COPD, and, furthermore, indicate that patients who are normocapnic in the stable state can develop similar levels of hypercapnia during exacerbations as those with chronic hypercapnia.

Acute Disease↗

Dietary calcium as a statistical determinant of spinal trabecular bone density in amenorrhoeic and oestrogen-replete athletes.

A study investigating the relationship between spinal trabecular bone density (measured by QCT), dietary calcium (measured by questionnaire) and menstrual status in 67 elite female athletes was undertaken. Twenty-five athletes were amenorrhoeic, 27 eumenorrhoeic and 15 were taking an oral contraceptive. The mean bone density was significantly lower (P less than 0.0001) in the amenorrhoeics (168 mg/cm3; 95% confidence interval 154-182) than in the eumenorrhoeics (211 mg/cm3; 197-224) and oral contraceptive takers (215 mg/cm3; 197-233). There was also a significant positive linear correlation between trabecular bone density. However, factors with which calcium intake may be linked, such as energy intake and expenditure, were not measured and therefore it is possible that this relationship is indirect. Further studies on the relationship between dietary calcium and bone mineral density in young women are needed.

Adolescent↗

Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes.

OBJECTIVE: To study the effects of amenorrhoea and intensive back exercise on the bone mineral density of the lumbar spine in female athletes. DESIGN: Cross sectional study comparing amenorrhoeic with eumenorrhoeic athletes and rowers with non-rowers. SETTING: The British Olympic Medical Centre, Northwick Park Hospital. PATIENTS: 46 Elite female athletes comprising 19 rowers, 18 runners, and nine dancers, of whom 25 were amenorrhoeic and 21 eumenorrhoeic. MAIN OUTCOME MEASURE: Trabecular bone mineral density of the lumbar spine measured by computed tomography. RESULTS: Mean trabecular bone mineral density was 42 mg/cm3 (95% confidence interval 22 to 62 mg/cm3) lower in the amenorrhoeic than the eumenorrhoeic athletes; this difference was highly significant (p = 0.0002). Mean trabecular bone mineral density was 21 mg/cm3 (1 to 41 mg/cm3) lower in the non-rowers than the rowers; this was also significant (p = 0.05). There was no interaction between these two effects (p = 0.28). CONCLUSION: The effect of intensive exercise on the lumbar spine partially compensates for the adverse effect of amenorrhoea on spinal trabecular bone density.

Adult↗