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Mallon P.W.G.,University College Dublin | Mallon P.W.G.,Materials Misericordiae University Hospital
Current Opinion in Infectious Diseases | Year: 2010

PURPOSE OF REVIEW: This review details the clinical aspects and pathogenesis of low bone mineral density (BMD) in HIV, discusses broad management issues and outlines areas in which our understanding of this condition is incomplete. RECENT FINDINGS: Low BMD is prevalent in HIV-infected patients, with traditional risk factors, HIV infection and exposure to antiretroviral therapy all contributing. The role of specific antiretrovirals in the development of low BMD remains controversial, but most changes arise at either antiretroviral therapy initiation or switch. SUMMARY: Further research is needed to clarify mechanisms underlying low BMD in HIV, whether low BMD will translate to increased fractures and to determine the correct therapeutic approach to low BMD in HIV, particularly in younger HIV-infected patients. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Egan J.J.,Materials Misericordiae University Hospital
European Respiratory Review | Year: 2011

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal form of diffuse interstitial lung disease. Management of IPF requires an orderly approach, with regular evaluations and implementation of both pharmacological and nonpharmacological treatments. Pulmonary rehabilitation can relieve patients from the distressing symptoms of IPF and improve quality of life. Oxygen therapy is central to treatment of all patients. Lung transplantation enhances survival in selected patients. Mechanical ventilation may be used in patients with acute exacerbations, but the prognosis is poor in these cases. Palliative care focuses on symptom management, advance directives and end-of-life planning. Patient support groups may also play an important role. Copyright©ERS 2011.

Ryan J.D.,Materials Misericordiae University Hospital
Hepatology (Baltimore, Md.) | Year: 2010

Hereditary hemochromatosis (HH) is a common inherited iron overload disorder. The vast majority of patients carry the missense Cys282Tyr mutation of the HFE gene. Hepcidin, the central regulator of iron homeostasis, is deficient in HH, leading to unchecked iron absorption and subsequent iron overload. The bone morphogenic protein (BMP)/small mothers against decapentaplegic (Smad) signaling cascade is central to the regulation of hepcidin. Recent data from HH mice models indicate that this pathway may be defective in the absence of the HFE protein. Hepatic BMP/Smad signaling has not been characterized in a human HFE-HH cohort to date. Hepatic expression of BMP/Smad-related genes was examined in 20 HFE-HH males with significant iron overload, and compared to seven male HFE wild-type controls using quantitative real-time reverse transcription polymerase chain reaction. Hepatic expression of BMP6 was appropriately elevated in HFE-HH compared to controls (P = 0.02), likely related to iron overload. Despite this, no increased expression of the BMP target genes hepcidin and Id1 was observed, and diminished phosphorylation of Smad1/Smad5/Smad8 protein relative to iron burden was found upon immunohistochemical analysis, suggesting that impaired BMP signaling occurs in HFE-HH. Furthermore, Smad6 and Smad7, inhibitors of BMP signaling, were up-regulated in HFE-HH compared to controls (P = 0.001 and P = 0.018, respectively). CONCLUSION: New data arising from this study suggest that impaired BMP signaling underlies the hepcidin deficiency of HFE-HH. Moreover, the inhibitory Smads, Smad6, and Smad7 are identified as potential disruptors of this signal and, hence, contributors to the pathogenesis of this disease.

Casey P.,Materials Misericordiae University Hospital | Bailey S.,University of Central Lancashire
World Psychiatry | Year: 2011

Adjustment disorders are common, yet under-researched mental disorders. The present classifications fail to provide specific diagnostic criteria and relegate them to sub-syndromal status. They also fail to provide guidance on distinguishing them from normal adaptive reactions to stress or from recognized mental disorders such as depressive episode or post-traumatic stress disorder. These gaps run the risk of pathologizing normal emotional reactions to stressful events on the one hand and on the other of overdiagnosing depressive disorder with the consequent unnecessary prescription of antidepressant treatments. Few of the structured interview schedules used in epidemiological studies incorporate adjustment disorders. They are generally regarded as mild, notwithstanding their prominence as a diagnosis in those dying by suicide and their poor prognosis when diagnosed in adolescents. There are very few intervention studies.

Shields C.J.,Materials Misericordiae University Hospital | Tiret E.,University Pierre and Marie Curie | Winter D.C.,St Vincents University Hospital
Annals of Surgery | Year: 2010

Objective: This study aims to describe recent experience with rectal carcinoids in European and North American centers. Background: While considered indolent, the propensity of carcinoids to metastasize can be significant. Methods: Rectal carcinoid patients were identified from prospective databases maintained at 9 institutions between 1999 and 2008. Demographic, clinical, and histologic data were collated. Median follow-up was 5 years (range, 0.5-10 years). Results: Two hundred two patients were identified. The median age was 55 years (range, 31-81 years). The majority of tumors were an incidental finding (n = 115, 56.9%). The median tumor size was 10 mm (range, 2-120 mm). Overall, 93 (49%) tumors were limited to the mucosa or submucosa, 45 (24%) involved the muscularis propria, 29 (15%) extended into the perirectal fat, and 6 (3%) reached the visceral peritoneum. The primary treatment modalities were endoscopic resection (n = 86, 43%) and surgical extirpation (n = 102, 50%). Forty-one patients (40%) underwent a high anterior resection, whereas 45 (44%) underwent anterior resection with total mesorectal excision. Seven patients (7%) underwent Hartman's procedure, 7 (7%) underwent abdomino-perineal resection, and 6 (6%) had transanal endoscopic microsurgery, whereas 4 (4%) patients underwent a transanal excision. Multiple variable logistic regression analysis demonstrated that tumor size greater than 10 mm and lymphovascular invasion were predictors of nodal involvement (P = 0.006 and < 0.001, respectively), whereas the presence of lymph node metastases and lymphovascular invasion was associated with subsequent development of distant metastases (P = 0.033 and 0.022, respectively). The presence of nodal metastases has a profound effect upon survival, with a 5-year survival rate of 70%, and 10-year survival of 60% for node positive tumors. Patients with distant metastases have a 4-year survival of 38%. Conclusion: Tumor size greater than 10 mm and lymphovascular invasion are significantly associated with the presence of nodal disease, rendering mesorectal excision advisable. Transanal excision is adequate for smaller tumors. Copyright © 2010 by Lippincott Williams & Wilkins.

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