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Biomedical subjects

D C Ireland

Publications and source records attributed to D C Ireland.

At least 19 recordsLinked to original sources

Distal scaphoid excision after radioscaphoid arthrodesis.

Radioscaphoid and radioscapholunate arthrodeses are effective surgical procedures for the treatment of nonsalvageable and isolated radiocarpal arthritis. These procedures, however, limit wrist motion significantly as the immobile scaphoid bridges the remaining midcarpal joint. A cadaver study of radioscaphoid arthrodesis followed by distal scaphoid excision was undertaken. Range of motion after radioscaphoid K-wire fixation alone demonstrated a 58% decrease in the preoperative flexion-extension arc to 60 degrees. After distal scaphoid excision (with the radioscaphoid pins still in place) the flexion-extension arc increased to 122 degrees or 86% of the preoperative range of motion; most of the increase in motion occurred at the midcarpal joint. Distal scaphoid excision releases the midcarpal joint following radioscaphoid fixation and results in a significantly greater wrist motion. If the results of this cadaver study are extrapolated to clinical practice the addition of this step to the previously described procedures of radioscaphoid or radioscapholunate arthrodesis addresses their major limitation, restricted motion.

Adult↗

Improved detection of capripoxvirus in biopsy samples by PCR.

A simple test based on the polymerase chain reaction (PCR) was used to detect capripoxvirus DNA in tissue culture supernatants and biopsy samples. The identity of the PCR products was confirmed by restriction enzyme analysis. The test has greater sensitivity and good specificity compared to an antigen trapping enzyme-linked immunosorbent assay which uses a detector antibody raised against a recombinant capripoxvirus-specific antigen. The reagents for the PCR-based test are all available commercially and the test provides a valuable addition to the current methods of virus detection.

Animals↗

The prefabrication of a bone graft in a rat model.

The prefabrication of bone grafts in a rat model was investigated. In 26 Sprague-Dawley rats, free iliac crest bone graft was harvested, bivalved, and reinserted heterotopically into the groin, where it was closed around the mobilized superficial inferior epigastric vascular bundle. In half the animals, the vascular bundle remained in continuity as a flow-through pedicle (group 1); in the remaining animals, the pedicle was ligated and divided distal to the bone graft. All grafts were isolated from other tissues by a silicone sheet envelope. At 3 or 6 weeks, the grafts were re-explored and analyzed by India ink perfusion and histologic examination for evidence of viability and neovascularization. Three weeks after insertion, India ink perfusion of the group 1 and 2 grafts revealed neovascularization extending to the periphery of the graft, and histologic examination showed extensive new bone formation on endosteal, periosteal, and trabecular surfaces of the graft. Six weeks after insertion, creeping substitution had almost completely remodelled the cortical and cancellous bone of both group 1 and 2 grafts to create a viable vascularized bone graft on a pedicle. In 3 control nonvascularized grafts (free iliac cortical bone without an implanted pedicle), all pre-existing bone of the graft was dead 3 weeks after insertion, and only very limited new bone formation was present within the graft.

Animals↗

Genetic identification of antigens exposed in damaged endothelial cells as laminin-binding proteins.

A monoclonal antibody, D5G2, which reacts in a balloon angioplasty damage model with unfixed damaged but not with unfixed undamaged human endothelial cells, was used to screen a human endothelial cDNA library in an Escherichia coli/lambda gt11 expression system. Sequences of DNA inserts in D5G2+ phage clones matched those reported for a laminin-binding protein, LBP-32. Both D5G2 and purified laminin bound to a polypeptide of 55 kD on PVDF membranes carrying electrophoretically separated endothelial cell lysates, D5G2 also bound to recombinant LBP expressed in E. coli, and showed similar staining patterns on human and bovine endothelial cells to another characterized anti-LBP antibody. Increased staining of unfixed endothelial cells on detergent permeabilization suggests that D5G2 binds to intracellular laminin-binding protein made accessible by cell membrane injury. Antibodies to intracellular targets exposed by cell damage may be useful in anchoring therapeutic agents at sites of vascular damage.

Angioplasty, Balloon↗

Australian repetition strain injury phenomenon.

The industrial upper limb pain epidemic colloquially known as repetition strain injury rapidly increased in the early 1980s to peak in 1985. Its less precipitous decline coincided with an awareness that repetition strain injury was a nonphysical sociopolitical phenomenon and a corresponding loss of the pecuniary benefits enjoyed by the powerful vested interest groups. Although its protagonists incorrectly claimed that this was a new disease, the rise and fall of repetition strain injury followed its historical predecessors including telegraphists' wrist and writer's cramp. Those affected by this phenomenon, a clearly defined cohort, were all employees who were highly suggestible and engaged in menial repetitious tasks with little job satisfaction. These patients were differentiated from those with genuine work related injuries whose symptoms are reproducible, with physical signs easily defined, disease identifiable, and response to physical treatment predictable. Most patients with repetition strain injury genuinely suffered the symptoms of which they complained and made little secondary gain relative to the protagonists of repetition strain injury who had a vested interest. The similarities between Australian repetition strain injury in the 1980s and American cumulative trauma disorder in the 1990s is compelling.

Arm Injuries↗

Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein IIb/IIIa receptor antibody.

BACKGROUND: Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIIa antibody (AZ1) was adsorbed onto cellulose polymer-coated intracoronary stents to enhance their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody-eluting stents. METHODS AND RESULTS: Twenty-three polymer-coated stents with AZ1 antibody bound by passive adsorption (AZ1-eluting) were compared with 23 control polymer-coated stents adsorbed with either no antibody (base-polymer, n = 12) or isotype-matched irrelevant antibody (anti-CMV-eluting, n = 11) by implantation into balloon-damaged, flow-reduced iliac arteries of New Zealand White rabbits. In 13 animals (acute group), flow measurements were made with transit-time flow probes and platelet adhesion was ascertained by use of 111In-labeled autologous platelets. In the other 10 animals (chronic group), stent occlusion was assessed macroscopically after they were killed 28 days after stenting. Arteries with AZ1-eluting stents had significantly less platelet deposition (15.8 +/- 4.5 x 10(7)) than either base-polymer (32.1 +/- 4.3 x 10(7)) or anti-CMV-eluting (35.2 +/- 8.8 x 10(7)) controls (ANOVA, P < .0001). Compared with base-polymer or anti-CMV-eluting controls, arteries with AZ1-eluting stents showed a marked reduction in cyclic blood flow variation (P < .0001) and a significantly greater mean blood flow 2 hours after stent deployment (P < .0001). There was a significant improvement in the patency rate of AZ1-eluting stents compared with controls at both 2 hours (92% versus 46%, P = .034) and 28 days (100% versus 40%, P = .015). CONCLUSIONS: Platelet GP IIb/IIIa antibody eluting from polymer-coated stents reduces platelet deposition, improves blood flow, virtually abolishes cyclic flow variation, and improves patency rates after stent implantation in a rabbit iliac artery model. Its potential for reducing stent-related thrombosis in humans warrants further evaluation.

Adsorption↗

Diagnosis of respiratory virus infections using GACELISA of urinary antibodies.

Sensitive and specific methods are needed to diagnose respiratory virus infections using body fluids such as urine that, unlike blood samples, are readily obtained by non-invasive means. Immunoglobulin G antibody capture enzyme-linked immunosorbent assays were developed for detection of antibody rises to respiratory syncytial virus and influenza A/Taiwan (H1N1) after initial quantification and adjustment of urinary IgG concentration. Of 24 elderly subjects whose sera were assayed by the complement fixation test for antibody to RSV, seven had convalescent titres > or = 32, and five had > or = 4-fold rises in titre. Acute and convalescent urines for six of these seven subjects were tested for virus-specific urinary IgG by GACELISA. Four of four persons with > or = 4-fold rises in CFT had urine ELISA convalescent to acute ratios of > or = 1.8 whereas two subjects with convalescent CF titres > 16, but no increase in serum antibody titre, had urine convalescent/acute ratios of 1.0. Ten subjects with > or = 4-fold rises in CFT or HI antibodies to influenza A/Taiwan had urine ELISA ratios of > or = 1.4 when samples taken on the day of influenza vaccination and 16 days later were compared. These preliminary observations demonstrate clinically significant rises in respiratory pathogen antibody levels between acute and convalescent urine samples, provided that total urinary IgG concentrations are quantified and then standardised.

Aged↗

Reverse radial artery fascial flap: a treatment for the chronically scarred median nerve in recurrent carpal tunnel syndrome.

Six patients underwent re-exploration of the carpal tunnel for symptoms of recurrent median nerve compression. All patients had previously undergone two or more decompressions. Operative findings revealed evidence of chronic scarring of the median nerve with flattening and perineural fibrosis. Following decompression together with neurolysis and tenosynovectomy, a vascularized fascial flap pedicled distally on the radial artery was used to envelop the median nerve. Follow-up studies of between 12 and 61 months (mean, 25 months) showed improvement of symptoms in all patients, with 2 patients describing complete relief of pain and paresthesia and 4 patients describing mild intermittent pain or paresthesia.

Carpal Tunnel Syndrome↗

Effects of upper respiratory tract infections in patients with cystic fibrosis.

BACKGROUND: The polymerase chain reaction has improved the detection of picornaviruses and rhinoviruses and our understanding of their role in reversible airways disease. The effects of colds on lower respiratory morbidity and bacterial colonisation in cystic fibrosis remain uncertain. METHODS: Children with cystic fibrosis were evaluated regularly in the clinic and the parents notified the investigators when their child developed a cold. Nasopharyngeal specimens were collected at the start of the infection for polymerase chain reaction, bacteriology was also undertaken and again three weeks later, and pulmonary function was measured in children aged > or = 6 years at four day intervals for three weeks. The effects of colds on rate of progression of cystic fibrosis were assessed by pulmonary function, Shwachman scores, and radiology. RESULTS: Thirty eight children suffered 147 colds over 17 months. Picornaviruses were detected in 51 (43%) of 119 nasopharyngeal specimens, and 21 of the 51 were further identified as rhinoviruses. Pulmonary dysfunction was similar following picornavirus and non-picornavirus infections; the mean change from baseline in forced expiratory volume in one second (FEV1) was -16.5% and -10.3% at 1-4 days and 21-24 days, respectively, after onset of a cold. Children who experienced more colds than average had evidence of disease progression with reduction in Shwachman score, increasing Chrispin-Norman score, and greater deterioration in FEV1 per annum. Ten of 12 new bacterial infections were associated with a cold. CONCLUSIONS: Picornavirus and non-picornavirus colds are associated with pulmonary function abnormalities and disease progression in patients with cystic fibrosis, and predispose to secondary bacterial infection and colonisation.

Adolescent↗

Bronchial inflammation and the common cold: a comparison of atopic and non-atopic individuals.

BACKGROUND: Cold virus infections are associated with asthma attacks and with increased bronchial responsiveness even in normal subjects. Possible mechanisms include epithelial damage, interaction with adhesion molecules or with T-helper cell subsets. OBJECTIVE: To determine whether colds increase lower airway inflammation, comparing atopic with non-atopic normal subjects. METHODS: Thirty healthy volunteers (15 atopic) took part. Baseline tests included viral serology, microbiological culture and polymerase chain reaction for rhinovirus infection (HRV-PCR), histamine bronchial provocation and bronchoscopy. Twenty subjects (eight atopic) underwent repeat tests when they developed a cold. RESULTS: Forced expiratory volume in one second (FEV1) was significantly lower during colds (-0.19 L [95% confidence interval -0.10, -0.29], P = 0.0004) and there was a significant increase in bronchial responsiveness (+0.62 doublings of the dose-response slope [+0.24, +1.00], P = 0.003). Eight subjects (two atopic) had a diagnosed viral infection: two HRV, three coronavirus (HCV), one HRV + HCV, one parainfluenza III (PI) and one respiratory syncytial virus (RSV) (also Haemophilus influenzae). In biopsies, during colds, total eosinophils (EGI+) increased significantly (geometric mean 6.73-fold [1.12,40.46], P = 0.04). Activated eosinophils (EG2+) only increased significantly in the subgroup without diagnosed viral infection and particularly in atopic rhinitics. T-suppressor (CD8+) cells also increased significantly (median + 178.3 cells mm2, P = 0.004). Epithelial expression of intercellular adhesion molecule-1 (ICAM-1) expression increased in four atopic rhinitics during colds. Bronchial washings showed a significant increase in neutrophils (GM 1.53-fold [1.04,2.25], P = 0.02). CONCLUSION: Lower airway inflammation was present in atopic and non-atopic normal subjects with colds. Atopic subjects differed in that they were less likely to have positive virological tests and were more likely to show activated eosinophilia in the lower airway, despite a similar spectrum of symptoms.

Adolescent↗

Respiratory viruses and exacerbations of asthma in adults.

OBJECTIVE: To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN: Longitudinal study of 138 adults with asthma. SETTING: Leicestershire Health Authority. SUBJECTS: 48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES: Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS: Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS: These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.

Adult↗

Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF.

We have used protection against ribonuclease H to investigate the mechanisms by which U1 small nuclear ribonucleoprotein particles (snRNPs) determine the use of two alternative 5' splice sites. The initial binding of U1 snRNPs to alternative consensus splice sites was indiscriminate, and on a high proportion of pre-mRNA molecules both sites were occupied simultaneously. When the sites were close, this inhibited splicing. We propose that double occupancy leads to the use of the downstream site for splicing and that this is the cause of the proximity effect seen with strong alternative splice sites. This model predicts that splicing to an upstream site of any strength requires a low affinity of U1 snRNPs for the downstream site. This prediction was tested both by cleaving the 5' end of U1 snRNA and by altering the sequence of the downstream site of an adenovirus E1A gene. The enhancement of downstream 5' splice site use by splicing factor SF2/ASF appears to be mediated by an increase in the strength of U1 snRNP binding to all sites indiscriminately.

Adenovirus E1A Proteins↗

Improved detection of rhinoviruses in nasal and throat swabs by seminested RT-PCR.

A seminested RT-PCR (nRT-PCR) was used to detect picornavirus (PV) RNA in cell cultures inoculated with rhinoviruses (HRVs) and enteroviruses (EVs). PCR tests in which a primary "touchdown" PCR was followed by secondary reactions using PV or HRV specific primers were able to differentiate HRVs of 48 serotypes from EVs. PVnRT-PCR and HRVnRT-PCR were then used to test nasal and throat swabs from adult subjects with naturally acquired respiratory virus infections. The swabs were also analysed for respiratory viruses by cell culture techniques and the rates of PV identification by the two methods were compared. PVnRT-PCR was found to be at least five times more sensitive than cell culture for the detection of PVs in these clinical specimens. Paired acute and convalescent serum samples were tested for complement fixing antibodies to adenovirus, influenza A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, and 3, Myco plasma pneumoniae, and Chlamydia psittaci. An enzyme-linked immunosorbent assay (ELISA) was used to detect rises in antibody level to coronavirus types 229E and OC43. The overall rate of pathogen identification in 159 swabs from adult asthmatics increased from 28% when only cell culture and serology were used to 57% when these methods were supplemented by PVnRT-PCR.

Adult↗

Intraosseous ganglion cyst of the lunate: diagnosis and management.

Intraosseous ganglion cyst of the lunate is an uncommon lesion and cause of wrist pain. Histopathologically it is identical to the common dorsal wrist ganglion and treatment by arthrotomy, curettage of the ganglion and bone graft resulted in clinical improvement in nine patients, six of whom became symptom-free.

Adult↗