Search PubMed⌕ Search

Biomedical subjects

J Egan

Publications and source records attributed to J Egan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Morphological and mechanical analysis of the glenoid by 3D geometric reconstruction using computed tomography.

OBJECTIVE: To provide a morphological and mechanical analysis of the glenoid by 3D geometric reconstruction using computed tomography. DESIGN: For patients with different pathologies (Group A=control group, Group B=primary osteoarthritis, Group C=rheumatoid arthritis), the variation in shape of the scapula was characterized by measuring the glenoid version (beta). METHODS: Mapping the computed tomography number and its 3D variation in the bone as a finite element structure. RESULTS: In Group A, the mean value of version was 17 degrees (range 12-22 degrees ). In Groups B and C the mean value of version were 27 degrees (range 4-48 degrees ) and 31 degrees (range 25-31 degrees ) of retroversion. At the center of the glenoid there was a homogeneous area of bony tissue with low computed tomography values and the subchondral bone could be clearly identified. For Group B patients, the computed tomography values were increased at the posterior margin of the glenoid, with a thickening of the posterior area acting as a strengthening column. For the Group C patients, the anatomical modifications were not reproducible between two cases examined. CONCLUSION: Results reveal a great difference between a healthy and a pathological glenoid. RelevanceThe method will be the basis for future study of the pathological characteristics of the joint. Results should provide a new pre-operative insight to help guide the surgeon.

Arthritis, Rheumatoid↗
PubMed2000

Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours.

Human bronchioloalveolar carcinoma (BAC) is a lung cancer, morphologically similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary adenomatosis (SPA) or jaagsiekte. SPA is caused by an exogenous type B/D retrovirus (jaagsiekte sheep retrovirus (JSRV)), which prompted the present study to obtain evidence of a retrovirus in BAC. A panel of 249 human lung tumours, 21 nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other organs and a cell line expressing a human endogenous retrovirus protein was examined immunohistochemically using a rabbit antiserum directed against the JSRV capsid protein. Specific staining was detected only in the cytoplasm of recognizably neoplastic cells in the pulmonary alveoli of 39 of 129 (30%) BACs, 17 of 65 (26%) lung adenocarcinomas and two of seven large cell carcinomas. The remaining samples were negative. These results support the hypothesis that some human pulmonary tumours may be associated with a jaagsiekte sheep retrovirus-related retrovirus, warranting further studies.

Adenocarcinoma↗
PubMed2000

Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family.

BACKGROUND: Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor beta (TGF-beta) family which plays a key role in cell growth, have recently been identified as causing familial PPH. We have searched for BMPR2 gene mutations in sporadic PPH patients to determine whether the same genetic defect underlies the more common form of the disorder. METHODS: We investigated 50 unrelated patients, with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension, by direct sequencing of the entire coding region and intron/exon boundaries of the BMPR2 gene. DNA from available parent pairs (n=5) was used to assess the occurrence of spontaneous (de novo) mutations contributing to sporadic PPH. RESULTS: We found a total of 11 different heterozygous germline mutations of the BMPR2 gene in 13 of the 50 PPH patients studied, including missense (n=3), nonsense (n=3), and frameshift (n=5) mutations each predicted to alter the cell signalling response to specific ligands. Parental analysis showed three occurrences of paternal transmission and two of de novo mutation of the BMPR2 gene in sporadic PPH. CONCLUSION: The sporadic form of PPH is associated with germline mutations of the gene encoding the receptor protein BMPR-II in at least 26% of cases. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, has important implications for patient management and screening of relatives.

Adolescent↗
PubMed2000

Investigation into the tribological condition of acetabular tissue after bipolar joint replacement hip surgery.

The aim of this research was to investigate the tribological condition of acetabular tissue before and after bipolar hip surgery. Articular cartilage was taken from the femoral head of patients undergoing primary joint replacement as a control. Tissue was also taken from the acetabular cups of patients undergoing revision hip surgery after primary bipolar surgery and compared with the control cartilage. The biomechanical characteristics of the two tissue types were tested using friction and compression tests. The friction tests were carried out on a sliding friction rig under nominal contact stresses of 0.5 and 4 MPa. The compression tests were carried out under a 0.8 MPa contact stress. The majority of the bipolar patients produced friction coefficients that were significantly higher than those produced by the control group, and the compression tests highlighted that the tissue from the bipolar patients produced a much greater rate of increase in displacement compared with the control cartilage. Histology showed major differences between the control cartilage and the bipolar tissue. The control cartilage showed a healthy collagen structure with a good distribution of proteoglycan whereas the majority of the bipolar tissue had lost tissue architecture and had a sparse fibrous structure. The high friction coefficients with the bipolar tissue imply that the frictional torque at the outer head of the bipolar prosthesis would be large compared with the inner bearing frictional torque. It was therefore predicted that the motion of the bipolar prosthesis should occur at the inner bearing.

Acetabulum↗
PubMed1999

Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes.

Nitric oxide (NO) donors were recently shown to produce biphasic contractile effects in cardiac tissue, with augmentation at low NO levels and depression at high NO levels. We examined the subcellular mechanisms involved in the opposing effects of NO on cardiac contraction and investigated whether NO modulates contraction exclusively via guanylyl cyclase (GC) activation or whether some contribution occurs via cGMP/PKG-independent mechanisms, in indo 1-loaded adult cardiac myocytes. Whereas a high concentration of the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 micromol/L) significantly attenuated contraction amplitude by 24.4+/-4.5% (without changing the Ca2+ transient or total cAMP), a low concentration of SNAP (1 micromol/L) significantly increased contraction amplitude (38+/-10%), Ca2+ transient (26+/-10%), and cAMP levels (from 6.2 to 8.5 pmol/mg of protein). The negative contractile response of 100 micromol/L SNAP was completely abolished in the presence of the specific blocker of PKG KT 5823 (1 micromol/L); the positive contractile response of 1 micromol/L SNAP persisted, despite the presence of the selective inhibitor of GC 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 micromol/L) alone, but was completely abolished in the presence of ODQ plus the specific inhibitory cAMP analog Rp-8-CPT-cAMPS (100 micromol/L), as well as by the NO scavenger oxyhemoglobin. Parallel experiments in cell suspensions showed significant increases in adenylyl cyclase (AC) activity at low concentrations (0.1 to 1 micromol/L) of SNAP (AC, 18% to 20% above basal activity). We conclude that NO can regulate both AC and GC in cardiac myocytes. High levels of NO induce large increases in cGMP and a negative inotropic effect mediated by a PKG-dependent reduction in myofilament responsiveness to Ca2+. Low levels of NO increase cAMP, at least in part, by a novel cGMP-independent activation of AC and induce a positive contractile response.

Actin Cytoskeleton↗
PubMed1999

Transforming growth factor beta (TGF-beta) and obliterative bronchiolitis following pulmonary transplantation.

BACKGROUND: Obliterative bronchiolitis (OB) characterised by small-airway fibrosis is a major cause of morbidity and mortality after lung transplantation. TGF-beta has been implicated in the pathogenesis of fibrosis. METHODS: We immunohistochemically examined 380 transbronchial biopsies (from 91 pulmonary transplants) using TGF-beta polyclonal antibodies. OB and interstitial fibrosis were diagnosed and graded in all biopsies. Other potential histologic and clinical risk factors for OB were analysed. RESULTS: Procedures were heart and lung (n = 32), bilateral sequential lung (n = 18), and single lung transplantation (n = 41). The incidence of OB in this group was 28.5%. In all patients with OB, TGF-beta was immunolocalized in the airways and lung parenchyma. TGF-beta expression was greater in OB patients (median score 8, range 5-12) in comparison to patients without OB (median score 4, range 1-13), p < .0001. Positive TGF-beta staining preceded the histologic confirmation of OB by 6 to 18 months. The development of OB was associated with two HLA mismatches at the A locus (p = .02); recurrent acute rejection episodes (p < .0005); lymphocytic bronchiolitis (p = .0001); and tissue eosinophilia, regardless of the rejection grade (p < .0001). CONCLUSIONS: Increased expression of TGF-beta is a risk factor for the development of OB. Other risk factors are recurrent acute rejection, lymphocytic bronchiolitis, tissue eosinophilia, and two mismatches at the HLA-A locus. This suggests that the pathogenesis of progressive small airway fibrosis characteristic of OB may be inflammatory damage, followed by an aberrant repair process due to excessive TGF-beta production following allograft injury. Hence, modulation of TGF-beta levels or function by antagonists may represent an important approach to control OB.

Adult↗
PubMed1999

Study of restriction fragment length polymorphism analysis and spoligotyping for epidemiological investigation of Mycobacterium bovis infection.

Restriction fragment length polymorphism (RFLP) analysis with probes derived from the insertion element IS6110, the direct repeat sequence, and the polymorphic GC-rich sequence (PGRS) and a PCR-based typing method called spacer oligonucleotide typing (spoligotyping) were used to strain type Mycobacterium bovis isolates from the Republic of Ireland. Results were assessed for 452 isolates which were obtained from 233 cattle, 173 badgers, 33 deer, 7 pigs, 5 sheep, and 1 goat. Eighty-five strains were identified by RFLP analysis, and 20 strains were identified by spoligotyping. Twenty percent of the isolates were the most prevalent RFLP type, while 52% of the isolates were the most prevalent spoligotype. Both the prevalent RFLP type and the prevalent spoligotype were identified in isolates from all animal species tested and had a wide geographic distribution. Isolates of some RFLP types and some spoligotypes were clustered in regions consisting of groups of adjoining counties. The PGRS probe gave better differentiation of strains than the IS6110 or DR probes. The majority of isolates from all species carried a single IS6110 copy. In four RFLP types IS6110 polymorphism was associated with deletion of fragments equivalent in size to one or two direct variable repeat sequences. The same range and geographic distribution of strains were found for the majority of isolates from cattle, badgers, and deer. This suggests that transmission of infection between these species is a factor in the epidemiology of M. bovis infection in Ireland.

Animals↗
PubMed1998

Investigation into the effects of proteins and lipids on the frictional properties of articular cartilage.

The aim of this study was to investigate the effects of the proteins and the lipids on the frictional properties of articular cartilage in the mixed and boundary lubricating regimes. Bovine articular cartilage that had been treated to remove the lipids, and cartilage that had been treated to remove the proteins, from the surface layer were studied in order to investigate differences in their lubricating abilities. Tests were carried out on a sliding friction rig under contact pressures of 0.5 and 4 MPa. The results of the friction tests carried out under the 4 MPa contact pressure showed a slight increase in friction coefficient for both the lipid and the protein deficient cartilage when compared with the control cartilage. These differences were more apparent at the shorter loading times but none of the differences were found to be statistically significant. The tests at the lower contact pressure of 0.5 MPa showed that removing the lipids by washing the surface with detergent increased the friction coefficient at the shorter loading times but had no effect at the longer loading times. Digesting the cartilage with trypsin to remove the proteins from the surface layer had no effect on the friction coefficient at the shorter loading times but reduced the friction coefficient at the longer loading times. Both these results were confirmed with specimens that had both the lipids and the proteins removed from the surface layer.

Animals↗
PubMed1998

Transforming growth factor-beta1 and lung allograft fibrosis.

OBJECTIVES: Transforming growth factor beta1 (TGF-beta1) is a potent immunosuppressive cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components. The repair process following lung allograft injury is due to rejection or infection replaces lung parenchyma by fibrotic tissue, leading to pulmonary dysfunction. The role of TGF-beta1 in this excessive healing process and increasing the risk of infection is unknown. METHODS: We analysed our patient data to investigate the relevance of different factors on allograft fibrosis and its correlation with TGF-beta1. Fibrosis was graded in H and E stained sections. TGF-beta1 genotype was determined in all patients. RESULTS: Patients were aged between 16 and 62 years (mean age of 39.6 years). Procedures were heart/lung (n = 32), double lung (n = 18), and SLT (n = 41). A total of 46 patients had lung allograft fibrosis diagnosed in transbronchial biopsies sections. Patients who had developed interstitial fibrosis had significantly more acute rejection episodes (mean 3.4 +/- 2.8) compared with patients without fibrosis (mean 2.1 +/- 2.2) (P = 0.024). The presence of eosinophils in the interstitium preceded and were associated with the development of fibrosis regardless of the rejection grade (P = 0.0001). TGF-beta1 was heavily expressed in sections with fibrosis with a mean score of 6.8 +/- 2.9 compared with 2.4 +/- 0.6 in sections with no fibrosis (P < 0.0001). TGF-beta1 expression correlated positively with fibrosis grades (P < 0.0001). The mean survival for patients with a fibrosis score > 6 is 892.4 +/- 73 days compared with mean survival 427 +/- 78 in patients with scores < 6 (P = 0.0001). Patients who developed fibrosis had homozygous TGF-beta1 genotype that correlates with excessive TGF-beta1 expression (P = 0.01). The use of cardiopulmonary bypass was associated with the development of excessive fibrosis (P = 0.02), and 7 patients who had severe fibrosis died of septicaemia (17.5%). FEV1 (forced expiratory volume) was significantly higher in patients without fibrosis (1870 +/- 111 ml versus 1590 +/- 160; P = 0.02). CONCLUSIONS: The risks of lung allograft fibrosis increases with recurrent rejection, tissue eosinophilia, homozygous TGF-beta1 genotype and the use of bypass machine. Fibrosis was associated with higher mortality and morbidity might be explained by the TGF-beta1 immunosuppressive and fibrotic properties. Immunological strategies to down-regulate TGF-beta1 production might improve survival and function of lung allografts.

Adolescent↗
PubMed1998

Differentiation of desquamative interstitial pneumonia (DIP) from pulmonary adenocarcinoma by immunocytochemistry.

AIM: After a misdiagnosis of pulmonary adenocarcinoma as desquamative interstitial pneumonia (DIP), we investigated whether immunohistochemical markers could differentiate these conditions. METHODS AND RESULTS: Three cases of DIP and one pulmonary adenocarcinoma masquerading as DIP were studied by light and electron microscopy. All cases were mucin-negative. The cases of DIP were CD68 positive but cytokeratin-negative. The adenocarcinoma was cytokeratin-positive (AE1/3 and CAM5.2), as well as showing some CD68-positive cells. Markers for carcinoma (CEA, Ber-EP4, and Leu M1) were negative in all cases. Ultrastructurally the adenocarcinoma appeared to be derived from Type II pneumocytes. CONCLUSION: Before a diagnosis of DIP is made, cytokeratin markers should be used.

Adenocarcinoma↗
PubMed1998

Investigation into the effect of proteoglycan molecules on the tribological properties of cartilage joint tissues.

The aim of this research was to investigate the role of the hydrophilic properties of the proteoglycan molecules within the cartilage matrix, on the tribological properties of joint tissues in the mixed and boundary lubricating regime. Bovine articular cartilage, bovine meniscus and bovine cartilage that had been degraded to remove the chondroitin sulphate from its proteoglycans were studied in order to investigate differences in their friction and compression responses. The tissues were tested on a sliding friction rig under nominal contact stresses of 0.5 and 4 MPa. The compression tests were carried out under a 0.8 MPa contact stress. The compression tests showed the cartilage and meniscus deforming at the same rates, but the degraded cartilage deformed more quickly to reach its equilibrium position in a shorter period of time. The friction tests carried out at a constant load revealed the friction of the meniscus rising more rapidly with loading time than the cartilage. The degraded cartilage followed an almost identical curve as the untreated cartilage. Although the reduced proteoglycan content of the degraded cartilage substantially altered the biphasic compression response, it did not have an effect on the frictional properties of the tissue.

Animals↗
PubMed1998

Single lung transplantation for emphysema: predictors for native lung hyperinflation.

BACKGROUND: Single lung transplantation is an established procedure for the treatment of respiratory failure resulting from emphysema. Initial concerns suggested that ventilation/perfusion mismatch may result in an unsatisfactory outcome, but good clinical results proved those concerns to be unfounded. However, a proportion of patients have had development of native lung hyperinflation (NLH), with increased morbidity and mortality rates. This study was undertaken to evaluate the factors that might predict those patients with emphysema who are at greatest risk for development of NLH. METHODS: We retrospectively analyzed data from 27 patients who underwent 31 single lung transplantations for emphysema. The patients were divided into two groups: group A, 12 patients with development of acute or chronic NLH, and group B, 15 patients without development of hyperinflation. NLH was defined as radiologic mediastinal shift with flattening of the ipsilateral diaphragm associated with respiratory dysfunction or hemodynamic instability. All preoperative and postoperative data from recipients and data from donors were analyzed. RESULTS: There were no differences between the two groups regarding age, preoperative partial pressure of oxygen, partial pressure of carbon dioxide, acid-base status, donor lung size and physiological structure, side of transplantation, primary pathologic condition, rejection score, infection episodes and obliterative bronchiolitis in the transplanted lung after operation. Patients with NLH had a significantly higher preoperative mean pulmonary artery pressure of 31.6 mm Hg (confidence interval [CI] 26.7 to 35.7), transpulmonary gradient of 20.5 mm Hg (CI 17.4 to 23.5), a lower mean forced expiratory volume in 1 second of 427 ml (CI 352 to 502), and higher mean residual volume of 4450 ml (CI 3769 to 5132). The duration of ventilation, 168 hours (CI 45 to 290), and the postoperative mean pulmonary artery pressure of 26 mm Hg (CI 23 to 28.7) are significantly higher in the hyperinflation group. Early death in group A (n = 5) was higher than in group B (no deaths) (p = 0.02). Six patients in group A required surgical treatment (two early native lung volume reductions, two early ipsilateral retransplantations, and two late contralateral transplantations). Group A patients tended to have poorer long-term lung function after transplantation, with reduced forced expiratory volume in 1 second, forced vital capacity, and higher residual volume (p = NS). CONCLUSION: Patients with end-stage emphysema and relative pulmonary hypertension, severe airway obstruction, and air trapping are at greatest risk for development of early and late NLH. In this subgroup of patients, an alternative treatment strategy may be considered.

Diaphragm↗
PubMed1997

Isolation of mycobacteria from lymph node lesions in deer.

A total of 14,842 farmed deer were slaughtered and examined postmortem in Irish abattoirs between January 1993 and September 1996. Lymph node lesions were detected in 119 deer and these were examined histopathologically and cultured. A total of 115 of the lesions were characterised as tuberculous and, on culture, Mycobacterium avium was isolated from 49 of them, M bovis from 41, unclassified mycobacteria from five, and 20 of the tuberculous lesions did not yield any isolate. Tubercles which yielded M avium on culture contained on average more acid-fast bacilli, more epithelioid macrophages and fewer Langhans giant cells than tubercles from which M bovis was isolated. Twelve lesions from feral deer culled from a national park were also examined and M bovis was isolated from nine.

Animals↗