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D O'Shea

Publications and source records attributed to D O'Shea.

At least 19 recordsLinked to original sources
PubMed2006

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.

Adolescent↗
PubMed2006

Smoking and thyroid-associated ophthalmopathy: A novel explanation of the biological link.

INTRODUCTION: Cigarette smoking is the strongest modifiable risk factor for developing thyroid-associated ophthalmopathy (TAO), and the severity of TAO is related to the current number of cigarettes smoked per day. We aimed to establish the effects of cigarette smoke extract (CSE) on an in vitro model of TAO. METHODS: Orbital tissue was taken during surgery from 10 patients with TAO and nine control subjects. Orbital fibroblasts were cultured and exposed to CSE, and intercellular adhesion molecule 1 (ICAM1) expression was measured by flow cytometry. Glycosaminoglycan production was measured by hyaluronic acid ELISA. Orbital fibroblasts were grown in adipogenic media with or without CSE and/or IL-1, and the degree of adipogenesis was quantified. RESULTS: Fibroblasts from patients with TAO and controls showed similar responses. ICAM1 expression was not affected by CSE. Hyaluronic acid production was stimulated by CSE in a dose-dependent manner (correlation coefficient, 0.978; P = 0.022), with 5% CSE causing an increase of 44% (P = 0.001). CSE increased adipogenesis in a dose-related manner, as did IL-1. The effects of CSE and IL-1 on adipogenesis were synergistic, with the degree of adipogenesis in the well containing both 5% CSE and 0.1 ng/ml IL-1 being double the magnitude of the sum of the values obtained from either stimulus alone (P < 0.001). Addition of an anti-IL-1 antibody to the well containing both 5% CSE and 0.1 ng/ml IL-1 reduced the degree of adipogenesis by 82% (P < 0.001). CONCLUSION: These findings may help explain how cigarette smoking has a detrimental effect in TAO and suggests that IL-1 may be an attractive therapeutic target in TAO.

Adipogenesis↗
PubMed2006

Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: a single-centre experience in 211 patients.

High-dose therapy with autologous stem cell therapy (ASCT) has become the treatment of choice for eligible patients with myeloma. We analysed retrospectively the prognostic influence of pre-transplant characteristics and transplant modalities on response and survival in 211 myeloma patients who were transplanted in our centre between 1994 and 2004. All patients received peripheral blood stem cell support after conditioning with melphalan alone (183 patients), or melphalan and total blood irradiation (28 patients). We evaluated the influence of age, type of multiple myeloma, status prior and post ASCT, previous treatment regimens, time of ASCT from diagnosis, year of autograft, dose of re-infused CD34(+) cells, plasma cell infiltration and beta2-microglobulin at diagnosis on overall survival (OS) and event-free survival (EFS) to define patients with better prognosis. Median OS and EFS from transplantation were 50.9 and 20.1 months, respectively. Median OS from diagnosis was 68.8 months. Transplant-related mortality was 1.4%. Lower beta2-microglobulin levels, achievement of complete remission (CR) post transplant and lower plasma cell infiltration at diagnosis and transplant correlated with longer EFS and OS, whereas CR at transplant and low international prognostic index at transplant correlated with better EFS. Higher CD34(+) cell dose correlated with improved OS. We conclude that ASCT is safe and effective and the outcome is independent of age, time from diagnosis, previous treatment and conditioning regimen.

Adult↗
PubMed2006

The effects of tumour necrosis factor-alpha and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis.

OBJECTIVE: Cytokines are likely to play a key pathogenic role in thyroid-associated ophthalmopathy (TAO). Anti-cytokine therapy has been proposed to be a possible treatment for active TAO. We aimed to establish the effects of selected cytokines on intercellular adhesion molecule 1 (ICAM1) expression, glycosaminoglycan (GAG) production and adipogenesis in orbital fibroblasts (OFs) from patients with TAO. METHODS: Orbital tissue was taken during surgery from eight patients with TAO and five control subjects. OFs were cultured and ICAM1 expression measured by flow cytometry. GAG production was measured by hyaluronic acid ELISA. OFs were grown in adipogenic media and the degree of adipogenesis quantified. RESULTS: Responses were similar in OFs from patients with and without TAO. Tumour necrosis factor-alpha (TNFalpha) and interleukin1 (IL1) (0.1 ng/ml) stimulated ICAM1 expression by eight- to ten-fold. Anti-cytokine agents inhibited the cytokine-upregulated ICAM1 expression by 90-99% (P<0.01). TNFalpha and IL1 (0.1 ng/ml) increased hyaluronic acid production by 44 and 95% (P<0.01) respectively. Anti-cytokine agents inhibited these responses by 79-138% (P<0.04).0.013 AU and -1.0; P<0.03) whilst IL1 (0.1 ng/ml) stimulated adipogenesis (+0.05 AU and +5.7; P<0.02) measured by oil-red-O extraction and visual assessment respectively. The anti-IL1 agent inhibited IL1-mediated adipogenesis by 69-106% (P<0.04). CONCLUSION: TNFalpha and IL1 stimulate ICAM1 expression and GAG production, but have opposite effects on adipogenesis in OFs in vitro. IL1 promotes adipogenesis and its effects can be blocked by anti-IL1 agents in vitro. These agents may be the anti-cytokine treatment of choice for clinical trials in active TAO.

Adipogenesis↗
PubMed2006

Cystic fibrosis-related diabetes in adults.

We aimed to examine the differences between patients with cystic fibrosis-related diabetes (CFRD), and those with normal glucose handling in adults with cystic fibrosis (CF) in Ireland. We conducted a retrospective analysis of patients who attend the national referral centre for adult CF. Patients were diagnosed as having CFRD by the American Cystic Fibrosis Foundation criteria for diagnosis of CFRD. Of 259 patients, 150 were classifiable and 81 (54%) were classified as having CFRD. The groups with and without CFRD were not significantly different with regard to age (median 28.4 vs 26.0 years), sex (males 56% vs 55%) or BMI (median 20.9 vs 21.3 kg/m2). The group with CFRD had poorer lung function (mean % predicted FEV1 49.9 vs 66.4, P < 0.001), poorer bone mineral density (T-scores at the lumbar spine -1.95 vs -1.44, P < 0.05 and femur -1.19 vs -0.57, P < 0.01) and a greater proportion of PSEUDOMONAS AERUGINOSA positive sputum cultures (82.5% vs 64.2%, P < 0.05). No patients with CFRD carried the R1 17H mutation whilst 19% of the group without CFRD were heterozygous for this defect (P < 0.001). In conclusion, CFRD was highly prevalent in adults. The presence of CFRD was associated with poorer lung function, poorer bone mineral density and an increased prevalence of PSEUDOMONAS AERUGINOSA in sputum. The R1 17H mutation may be protective for CFRD.

Adult↗
PubMed2006

Gender identity disorder.

Gender Identity Disorder (GID) is a relatively rare condition of atypical gender development in which there is a psychological perception of self as masculine or feminine which is incongruent with ones phenotype. GID replaced the term Transsexualism in DSM-IV in 1994. The demographics of GID in Ireland have not been established. Since 2000 we have received 52 referrals of individuals with confirmed GID to our endocrine service for consideration for hormonal treatment (HT). Of the 52 patients 45 have male to female (MTF) GID (mean age 38.9 years) and 7 have female to male (FTM) GID (mean age 30.7 years). The age at presentation in this group is approximately 9 years older than in international series for both MTF (39 years v 30yrs) and FTM (31 yrs v 22yrs). The karyotype where analysed has been normal for their phenotypic sex. Twenty-three of the patients had received HT prior to attending our clinic that in only one case had been prescribed by a specialist. A number of patients had obtained HT via the internet or from overseas sources without medical review. Eighteen of the patients have been or are married and 14 of the group have children. The scale of referrals confirms that GID exists in the Irish population to a significant degree. Thus an appropriate care pathway for people with the condition needs to be established. This will facilitate optimum medical management of the patient group and a coherent approach to the many difficult social issues faced individuals with this disorder.

Adult↗
PubMed2005

Oral bisphosphonates improve Bone Mineral Density in adults with cystic fibrosis.

In adults with Cystic Fibrosis (CF) we sought to establish the effect of oral bisphosphonate therapy. Bone densitometry measured by dual energy X-ray absorptiometry (DXA), and clinical patient data, were reviewed retrospectively. Eighty-one patients (median age 27 years) had baseline and follow-up DXA, with an interval of 19.2 +/- 7.1 months. Thirty-six patients were treated with bisphosphonates (alendronate=23 and risedronate=13). Median follow-up Bone Mineral Density in the bisphosphonate group was 3.7% greater at the lumbar spine (95%CI 1.9 to 5.7%, P<0.0005) and 2.4% greater at the femur (95%CI 0.8 to 3.9%, P<0.005) than the group not treated with bisphosphonates. Oral bisphosphonate therapy had a beneficial effect on BMD in adults with CF.

Administration, Oral↗
PubMed2003

In a population study, can parathyroid hormone aid the definition of adequate vitamin D status? A study of people aged 65 years and over from the British National Diet and Nutrition Survey.

The British National Diet and Nutrition Survey of people aged 65 years and over in 1994-5 provided nationally representative estimates of food and nutrient intakes and biochemical status indices. In a further analysis study, parathyroid hormone (PTH) concentrations were measured in plasma samples from 773 subjects and were analyzed with the existing data on vitamin D intake, plasma 25-hydroxyvitamin D (25OHD), total plasma calcium and albumin. As predicted, a strong inverse relationship was observed between PTH and 25OHD. In the free-living respondents aged 65-84 years (n=507) there was a continuous decline in PTH with increasing 25OHD and no plateau, whereas in free-living people aged 85+ years (n=86) there was a significant deviation from a simple inverse relationship, with unexpectedly high PTH values in some people with satisfactory 25OHD status. There was a relationship between both PTH (inverse) and plasma 25OHD (direct) with calcium intake. A direct relationship between 25OHD and total plasma calcium was not significant when calcium was corrected for albumin. Geographically, 25OHD, and to a lesser extent PTH, exhibited a north-south gradient, and 25OHD was associated with self-reported health status. Both 25OHD and PTH were associated with self-reported physical activity. Low calcium intake and 25OHD was associated with receipt of state benefits. The relationship between plasma 25OHD and vitamin D intake revealed a striking seasonal cycle. 25OHD was strongly influenced by vitamin D intake in the winter in free-living subjects, but this was not observed in the summer. In people living in institutions such as nursing homes, who are less likely to be exposed to sunlight throughout the year, plasma 25OHD levels were lower throughout the year.

Aged↗
PubMed2002

Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic--pituitary--adrenal axis.

OBJECTIVE: Assessment of the hypothalamic--pituitary--adrenal (HPA) axis relies on the interpretation of serum (total) cortisol in response to dynamic tests of the HPA axis. Most cortisol is bound to cortisol-binding globulin (CBG) and serum total cortisol levels are significantly affected by variation in CBG. We hypothesised that CBG variation significantly affects interpretation of dynamic tests of the HPA axis. DESIGN: We investigated the effect of CBG variation on the outcome of the 250 microg short Synacthen test (SST) in 30 healthy adults. METHODS: Blood was sampled at time -30, 0 (at which point Synacthen was given) and +30 min. CBG and total cortisol were measured at each time-point. Integrity of the HPA axis was confirmed by measurement of urine cortisol. RESULTS: We found that CBG varied significantly within individuals, falling from 51+/-3.4 to 43 +/-3.2 microg/ml (P<0.0001) on changing from standing to lying. Total cortisol levels strongly correlated with CBG (r=0.88, P<0.0001). Thirteen subjects had a +30 min total cortisol <550 nmol/l. In these subjects, the CBG levels at each time-point were significantly lower compared with subjects who had a +30 min total cortisol of >550 nmol/l (P<0.05). To correct for variation in CBG we calculated the total cortisol:CBG ratio and found no significant difference in the +30 min ratio between these two groups. CONCLUSION: CBG varies significantly within and between individuals. This is accompanied by changes in serum total cortisol large enough to affect the outcome of an SST and, by implication, other tests of the HPA axis.

Adrenal Glands↗
PubMed2000

Diagnostic yield and development of a neurocardiovascular investigation unit for older adults in a district hospital.

BACKGROUND: Dizziness, syncope, and falls are common occurrences in elderly people. Neurocardiovascular investigation units aim to detect those patients who fall due to disturbances of blood pressure control or cardiac conduction. Specialist units have a high diagnostic yield in the investigation of these problems. Does this translate to less specialized centers? We report on the diagnostic findings of a district general hospital neurocardiovascular investigation unit. METHOD: A total of 120 consecutive patients over the age of 65 presenting to a single geriatrician were assessed. After a full history and physical examination, patients underwent neurocardiovascular investigation: blood pressure and heart rate response to active stand, carotid sinus massage, and 30-minute head-up tilt. RESULTS: The 120 patients assessed had a mean age of 78 years (range 66-94 years); in this group, 85 were women. Of these patients, 23% presented with falls, 14% with blackouts, and 30% with dizziness. The remaining 33% had overlap of symptoms. Neurocardiovascular investigations produced a diagnosis in 57% of the patients: 22% had cardioinhibitory carotid sinus syndrome (CSS): 15% had vasodepressor CSS; 29% had orthostatic hypotension; and 3% had vasovagal syncope. Thirteen percent had more than one neurocardiovascular abnormality, and 18% had benign positional vertigo. Five patients had postural instability causing falls. Hyperventilation syndrome, aortic stenosis, dysrhythmia, cervical spondylosis, and epilepsy each accounted for one case. Seventeen percent of the subjects remained undiagnosed after integrated neurocardiovascular assessment. CONCLUSION: Management of falls requires access to neurocardiovascular assessment. It is feasible to provide such a service in the district general hospital setting, with a comparable diagnostic yield to tertiary referral centers.

Accidental Falls↗
PubMed2000

Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential.

OBJECTIVE: To assess the diagnostic value of supine and upright carotid sinus massage in elderly patients. DESIGN: Prospective controlled cohort study. SETTING: Three inner city accident and emergency departments and a dedicated syncope facility. PATIENTS: 1375 consecutive patients aged > 55 years presenting with unexplained syncope and drop attacks; 25 healthy controls. INTERVENTIONS: Bilateral supine carotid sinus massage, repeated in the 70 degrees head up tilt position if the initial supine test was not diagnostic of cardioinhibitory and mixed carotid sinus hypersensitivity. MAIN OUTCOME MEASURES: Diagnosis of cardioinhibitory or mixed carotid sinus hypersensitivity; clinical characteristics of supine v upright positive groups. RESULTS: 226 patients were excluded for contraindications to carotid sinus massage. Of 1149 patients undergoing massage, 223 (19%) had cardioinhibitory or mixed carotid sinus hypersensitivity; 70 (31%) of these had a positive response to massage with head up tilt following negative supine massage (95% confidence interval, 25.3% to 37.5%). None of the healthy controls showed carotid sinus hypersensitivity on erect or supine massage. The initially positive supine test had 74% specificity and 100% sensitivity; these were both 100% for the upright positive test. The clinical characteristics of the supine v upright positive subgroups were similar. CONCLUSIONS: The diagnosis of carotid sinus hypersensitivity amenable to treatment by pacing may be missed in one third of cases if only supine massage is performed. Massage should be done routinely in the head up tilt position if the initial supine test is negative.

Aged↗
PubMed2000

Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline.

We describe the case of a patient who developed depression following bilateral orchidectomy for cryptorchidism. He was treated with a conventional selective serotonin reuptake inhibitor antidepressant, but continued to take St John's wort (hypericum) against medical advice. He subsequently developed a manic episode. We discuss postulated modes of action of St John's wort and the possible aetiological importance of testosterone replacement and abnormal gonadotrophin levels in this case.

Administration, Oral↗