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Biomedical subjects

D Mulherin

Publications and source records attributed to D Mulherin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis.

OBJECTIVE: To examine the relative contribution of individual synovial cell populations to polyarticular destruction in rheumatoid arthritis (RA). METHODS: Serial measurements of disease activity and articular destruction, obtained prospectively in 28 RA patients followed for a mean of 5.8 years, were correlated with synovial cell populations quantified using immunohistochemical techniques. RESULTS: The mean radiologic score worsened (from 37 to 86; P = 0.0001) despite significant improvement in disease activity. Synovial lining layer cell depth and sublining layer macrophage, but no lymphocyte, cell counts correlated significantly with radiologic course. Detailed analysis of 11 patients demonstrated reduced synovial lining expression of CD14 compared with CD68 (P = 0.003), whereas sublining expression of CD14 and CD68 was equivalent. CONCLUSION: Synovial macrophage numbers correlated with articular destruction in RA. In addition, the study results provided further evidence that lining layer macrophages may represent a distinct subpopulation that is of importance in this process. These findings have implications for the development of new therapies for RA.

Adult↗
PubMed1996

Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ.

The contrast between clinical improvement and radiological deterioration in rheumatoid arthritis (RA) is striking. We characterized this relationship using serial disease activity measures and radiographs of hands and feet in 40 RA patients observed over 6 yr. All disease activity measures improved, including grip strength, Ritchie index (RI), haemoglobin and erythrocyte sedimentation rate (ESR) (all P < 0.0001). In contrast, articular erosion increased (P < 0.0001). Radiological change during the study correlated with RI (r = 0.49), haemoglobin (r = -0.56) and ESR (r = 0.53). Radiological status at review also correlated with these variables (r = 0.36, -0.44 and 0.36, respectively). Articular erosion continues in RA despite clinical improvement and is accelerated in those with evidence of continuing synovial inflammation, reflected in clinical and laboratory measures of disease activity. Since many therapies in RA suppress inflammation, but not erosion, these findings suggest that the pathogenesis of articular erosion may differ from that of synovial inflammation.

Adult↗
PubMed1996

The diagnosis of iron deficiency in patients with rheumatoid arthritis and anemia: an algorithm using simple laboratory measures.

OBJECTIVE: Anemia of chronic disorders (ACD) and iron deficiency are common features in rheumatoid arthritis (RA), but may be difficult to distinguish without marrow sampling, which is invasive, time consuming, and expensive. We sought simple laboratory measures that identified patients with absent marrow iron stores (iron deficiency). METHODS: 45 anemic patients with RA underwent marrow sampling in addition to a complete blood count and serum ferritin and iron saturation measurements. RESULTS: 47% of patients had iron deficiency. These patients had significantly lower mean corpuscular volume (MCV), serum ferritin, and iron saturation. A 3 step algorithm was developed using these laboratory variables to identify iron deficiency. This algorithm correctly classified 94% patients with iron deficiency and 85% with ACD. CONCLUSION: Our study demonstrates that iron deficiency may be reliably identified by measuring serum ferritin, MCV, and iron saturation in many patients with RA, thereby avoiding the trauma and expense of marrow sampling.

Adult↗
PubMed1993

Assessment of cognitive function in patients with systemic lupus erythematosus.

The spectrum of central nervous system manifestations of systemic lupus erythematosus (SLE) is very broad and has been found to include subtle subclinical cognitive dysfunction which may be detected only by the lengthy process of detailed neuropsychological evaluation. This study reports the value of estimating premorbid intelligence as a simple yet effective means of screening for subclinical cognitive dysfunction. Twenty one female patients with clinically quiescent SLE underwent neuropsychological examination at entry to the study. In all patients, this examination included measurement of full-scale intelligence quotient (IQ), verbal and performance IQ as well as verbal and visual memories. In addition, premorbid intelligence was estimated using the Schonell graded word reading test. Nine patients (43%) gave a history of neuropsychiatric (NP) disease. No difference was identified between the results of the neuropsychological evaluation in these 9 patients and in either the other SLE patients or in age and sex matched control patients. Sixteen patients were re-evaluated 1 year later. A comparison of measured full-scale IQ with the estimated premorbid intelligence identified a subgroup of 3 patients who demonstrated a significant reduction in intelligence. Unlike the other 13 patients, these 3 patients had multiple (3 or more) other features of cognitive impairment.

Cognition Disorders↗
PubMed1993

Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the most common of the connective tissue disorders and can involve virtually any organ in the body. It is associated with pleuropulmonary manifestations in well over 50% of cases. Pleuritis with or without pleural effusion is the most common manifestation and can be particularly troublesome to manage but is rarely life-threatening. More serious manifestations in the lung include acute lupus pneumonitis with or without alveolar haemorrhage, chronic lupus pneumonitis and pulmonary hypertension. These all contribute significantly to overall mortality in SLE. The association between SLE and the antiphospholipid syndrome, leading to venous thrombosis and pulmonary embolism, is well recognized. Up to 20% of all cases of SLE present in childhood and many of these have pulmonary features at presentation or during the course of their illness. Sepsis is one of the main causes of death in SLE and pulmonary sepsis in these often immunocompromised patients contributes a significant proportion. Several drugs can produce a clinical syndrome that has many of the clinical and immunological features of SLE. Pleuritis may be seen in up to half of these cases of drug induced SLE. The development of SLE and conditions such as sarcoidosis or asbestosis in the same patient may represent a simple coincidence but there is some evidence for a closer association between these disorders.

Humans↗
PubMed1993

Spontaneous in vitro production of rheumatoid factor during infectious exacerbations of cystic fibrosis: correlation with circulating immune complex levels.

Rheumatoid factor (RF) production has been demonstrated during infections, including infectious exacerbations of cystic fibrosis (CF). The aim of this study was to evaluate the relationship of RF production to infection, and examine the mechanisms involved. Serial peripheral blood mononuclear cell (PBMC) cultures with measurement of spontaneous production of IgM RF, IgA RF, total IgM and IgA, and measurement of serum levels of immune complexes were carried out during exacerbations of CF. The percentage of B cells expressing CD5 was examined in a second cohort of acutely infected CF patients, and related to IgM RF production. IgM RF production was significantly elevated during acute infection compared with convalescence (P < 0.05), stable CF subjects (P < 0.005) and normal controls (P < 0.05). IgM RF production did not correlate with total IgM production in the majority of patients, but was closely related to circulating immune complex levels in 8/10 subjects. IgA RF production did not increase significantly during infection, and did not correlate with total IgA or IgM RF production, or with circulating immune complex levels. CD5+ B cells were not increased in the CF group, and the percentage of CD5+ B cells did not correlate with IgM RF synthesis. These observations suggest that RF production during infection is specifically induced, possibly by immune complex autoimmunization, and is not simply the result of polyclonal B cell activation. Different patterns of IgM RF and IgA RF synthesis suggest different mechanisms of induction.

Acute Disease↗
PubMed1992

Cystic fibrosis in adolescents and adults. The coming of age of cystic fibrosis.

Cystic fibrosis (CF) is the commonest, fatal, autosomal recessive disorder and is associated with lung sepsis, pancreatic failure and elevated sweat electrolytes. The CF gene on chromosome 7 encodes a protein identified as CF transmembrane conductance regulator (CFTR) which regulates chloride ion transport in epithelial cell membranes. Almost 100 mutations have been identified in this gene which cause defective chloride-channel control. Recently, this abnormality has been reversed in affected CF cells in vitro by retrovirus-mediated transfer of a normal gene. Fifty years ago, most cases died in childhood, but now up to 80% reach adulthood. Chronic lung sepsis is the principal cause of death, and intensive antibiotic therapy with chest physiotherapy is used to control this. Advanced lung disease can be successfully treated by heart-lung transplantation. Nebulised recombinant DNase and antineutrophil elastase agents such as alpha-1-antitrypsin and secretory leucoprotease inhibitor are potentially promising new therapies. Pancreatic insufficiency is managed by high-calorie diets and enteric coated enzyme supplements. Other prominent gastrointestinal complications include meconium ileus equivalent, biliary cirrhosis and cholelithiasis. Specially dedicated CF centres have led to improved survival rates and allow experienced staff to treat the many complications of CF while promoting research in this multisystem disorder.

Adolescent↗
PubMed1991

Aminoglycoside induced ototoxicity in patients with cystic fibrosis.

The improved survival of cystic fibrosis (CF) patients is partly due to intensive treatment for their chronic infections. Treatment usually includes intravenous and nebulised aminoglycoside antibiotics and they receive a large cumulative dose of these antibiotics over their lifetime. There is little information in the literature on the prevalence of ototoxicity due to aminoglycoside in these patients. We performed pure tone audiometry on 43 CF patients aged 14-42 years. Seven (16%) had bilateral sensorineural hearing loss (SNHL) for high frequency sounds, consistent with aminoglycoside induced ototoxicity. However, only 2 of these patients had documented toxic serum levels in the past. The identification of bilateral SNHL in one in six adult CF patients is a cause for concern. It may be that the high cumulative dose of aminoglycosides received by these patients may be causing inner ear injury in the absence of specific episodes of toxic serum levels.

Adolescent↗
PubMed1991

Cystic fibrosis in adolescents and adults.

A cystic fibrosis (CF) clinic for adults was established in 1977. We have reviewed the data on 164 patients who attended between 1977 and 1989. Twenty four patients had died, 11 being over 20 years after time of death. Of the 140 patients still alive, 61% were male and 53% were aged over 20 years. Only 55% were diagnosed by 1 year and 88% by 10 years. Almost all patients had respiratory symptoms and sputum culture yielded Pseudomonas species in 69%. Other respiratory problems included major haemoptysis and pneumothorax, each in 10%. We found a wide range of respiratory impairment among older patients. Among 3 patients aged over 23 years the mean (+/- S.D.) percent predicted FEV1 and FVC were 53.3% (+/- 18%) and 71.4% (+/- 20%) respectively. Mean weight in this group was 92.5% (+/- 14) of predicted. Malabsorption occurred in most patients and meconium ileus equivalent occurred in most patients and meconium ileus equivalent occurred in 34%. Other complications were clinical hepatomegaly (16%), diabetes mellitus (9%) and arthropathy (20%). Most patients were taking continuous antibiotics by mouth (89%) and by nebuliser (48%), beta-2 agonists by inhaler (57%) and oral steroids (29%). Almost all were taking multivitamins, pancreatic replacement therapy and multiple nutritional supplements. The number of CF "bed days" grew 12 fold since 1979 and the mean stay in hospital was double the hospital mean. The economic impact was such that over 1/4 of the annual hospital antibiotic budget was expended on CF patients.

Adolescent↗
PubMed1990

Frequency of deletion 508 among Irish cystic fibrosis patients.

We estimate the incidence of cystic fibrosis in Ireland to be at least 1 case per 1838 live births. We have analysed DNA from 44 Irish CF patients for the presence of deletion 508, using the polymerase chain reaction. The deletion was found in 76% of their chromosomes, and approximately 58% of the patients are homozygous for this deletion. Our results are not significantly different from those found in Canadian or UK patient populations, in which frequencies are higher than those found in Southern European countries.

Chromosome Deletion↗
PubMed1990

Pseudomonas colonization in cystic fibrosis: lack of correlation with secretion of ABO blood group antigens.

In cystic fibrosis, a majority of patients develop persistent lifelong respiratory tract colonisation with pseudomonas aeruginosa while a minority do not appear to become colonised. There is some evidence that non-secretion of ABO Blood Group antigens into body secretions is a marker for susceptibility to certain gram negative infections. Therefore, we studied 47 adult patients with cystic fibrosis to identify an association, if any, between secretor status and the presence or absence of pseudomonas aeruginosa in their sputum. Overall, we found no difference between the prevalence of non-secretors in our patient group and in the normal population. Furthermore, there was no association between secretor status and presence or absence of pseudomonas aeruginosa in sputum. We conclude that secretor status is unlikely to play a major role in susceptibility to pseudomonas aeruginosa infection in patients with cystic fibrosis.

ABO Blood-Group System↗
PubMed1990

Skin reactivity to atypical mycobacteria in cystic fibrosis.

Atypical mycobacterial disease has been described in a small number of patients with cystic fibrosis. Apart from one uncontrolled study, there is little information regarding atypical mycobacterial skin reactivity in this group of patients. We evaluated delayed cutaneous hypersensitivity to purified extracts of Mycobacterium avium, Mycobacterium intracellular, Mycobacterium kansasii and Mycobacterium bovis in 23 healthy controls and 43 adult and adolescent patients with cystic fibrosis. Fifteen of the cystic fibrosis group were receiving regular corticosteroids. Additionally, direct smear examination and Lowenstein Jensen culture were performed on sputum from the cystic fibrosis group. The prevalence of positive skin reactions was similar in the group with cystic fibrosis (30%) and in the control group (57%). Subgroup analysis showed that those cystic fibrosis patients receiving corticosteroids had a markedly lower prevalence of positive reactions (7%) compared to controls (P less than 0.01). When this subgroup was excluded from analysis, the prevalence of positive skin reactions among patients with cystic fibrosis was 43%. In the prospective sputum bacteriology study, one of the 43 cases grew Mycobacterium avium-intracellulare and had clinical and radiological evidence of this disease. Of note, this patient showed positive skin tests to all four mycobacterial species tested. Our data show no difference in the prevalence rate of positive skin reactions to atypical mycobacterial antigens between a control population and an adult cystic fibrosis population. In addition, the predictive value of skin testing is low in cystic fibrosis due to the high prevalence of cross-reactivity between different mycobacterial species and the high prevalence of anergy among those patients with advanced disease receiving treatment with corticosteroids.

Adolescent↗
PubMedDate not supplied

High resolution computed tomography in cystic fibrosis: correlation with pulmonary function and assessment of prognostic value.

OBJECTIVE: To assess the correlation between HRCT and pulmonary function in patients with CF. Further, to assess the prognostic value of HRCT in these patients. SUBJECTS AND METHODS: Clinical examination, chest radiographs and HRCT scans on 30 CF patients with an average age of 17 were scored using established scoring systems. The results were correlated with FEV1 and FVC both at time of CT scanning and after 30 months. Results were also correlated with the clinical progress of the patients over the follow-up period. RESULTS: HRCT, chest radiograph and clinical examination demonstrated similar correlation (p < 0.001) with FEV1 and FVC at the time of scanning. HRCT demonstrated the closest correlation with the clinical progress of the patients over the follow-up period and with follow-up pulmonary function. A maximum combined score for bronchiectasis and emphysema on HRCT seemed to indicate a poor prognosis. CONCLUSION: HRCT in CF patients correlates well with pulmonary function at time of scanning and at follow-up, and with clinical progress. There may be a role for CT in the identification of adolescent/adult patients who can be expected to need aggressive therapy in the future.

Adolescent↗