Cellular and molecular pathophysiology in the progression of Parkinson’s disease

Metabolic Brain Disease - Parkinson’s disease (PD) is a neurodegenerative disorder etiologically linked to the loss of substantia nigra (SN) dopaminergic neurons in the mid-brain. The...     

Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes

The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.     

Urinary tract infections: diagnosis and management in the emergency department

With the emergence of increasing resistance to common antibiotics used to treat urinary tract infections (UTIs), including ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX), the choice of antibiotics for these infections has become more challenging. In this article, the authors review the evidence-based guidelines for the evaluation and treatment of cystitis and pyelonephritis in the emergency department. They review the pathophysiology and describe the initial diagnostic workup, spending some time discussing the urine dipstick. The authors discuss whether hospital antibiograms are useful in making the initial antibiotic choice. The treatment section reviews the current recommendations and also highlights the use of nitrofurantoin in the treatment of uncomplicated UTIs. The authors also discuss the appropriate use of ciprofloxacin and TMP-SMX in the treatment of UTIs.     

Methicillin-resistant Staphylococcus aureus: A public health issue with economic consequences

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become endemic worldwide in hospitals, and community-associated MRSA is spreading into the community at large. OBJECTIVES: To estimate the current cost of MRSA in Canada and to assess the magnitude of this public health issue. METHODS: An extensive review of the literature was conducted to gather epidemiology, health care resource utilization and cost data for MRSA in Canadian settings. The current MRSA burden was estimated using available cost data and the most recent epidemiology data. RESULTS: The rate of MRSA in Canadian hospitals increased from 0.46 to 5.90 per 1000 admissions between 1995 and 2004, while community-associated MRSA continued to spread into the community. Patients harbouring MRSA required prolonged hospitalization (average 26 days of isolation per patient), special control measures, expensive treatments and extensive surveillance. Total cost per infected MRSA patient averaged $12,216, with hospitalization being the major cost driver (81%), followed by barrier precautions (13%), antimicrobial therapy (4%) and laboratory investigations (2%). The most recent epidemiological data, combined with available cost data, suggest that direct health care cost attributable to MRSA in Canada, including cost for management of MRSA-infected and-colonized patients and MRSA infrastructure, averaged $82 million in 2004 and could reach $129 million in 2010. CONCLUSION: MRSA is a costly public health issue that needs to be tackled if the growing burden of this disease in Canadian hospitals and in the community is to be limited.     

Paraumbilical collateral veins on MRI as possible protection against portal venous thrombosis in candidates for liver transplantation

BACKGROUND: We retrospectively evaluate the potential protective influence of patent paraumblical vein (PUV) collaterals against portal vein (PV) thrombosis and reduced PV diameter in candidates for orthotopic liver transplant (OLT) METHODS: Dynamic 3D contrast-enhanced MRI at 1.5T was obtained in 309 patients with cirrhosis without evidence of malignancy. All MR studies were reviewed by one reader for PUV collaterals, PV thrombosis and PV diameter. Statistical analysis was performed by Fisher exact tests; 50 selected studies were reviewed independently by two additional readers to determine interobserver agreement via intraclass correlation coefficient (ICC). RESULTS: Patent PUV was noted in 119 of 309 patients (38.5%). Mean PV diameter was 13.4 +/- 3.0 mm in patients with PUV compared with 11.3 +/- 3.6 mm without PUV (P < 0.01). Main PV thrombosis was present in 13 of 309 patients (4.2%) and significantly more frequent in those without PUV than with PUV (6.3% vs. 0.8%, P < 0.05). ICC indicated almost perfect agreement among three readers for presence of PUV collaterals (ICC = 0.91) and PV thrombosis (ICC = 0.96). CONCLUSION: Our results suggest that patients with patent PUV appear less likely to develop main PV thrombosis or small PV diameter, suggesting a protective effect of PUV on PV patency.     

Epidemiology of health and vulnerability among children orphaned and made vulnerable by HIV/AIDS in sub-Saharan Africa

The HIV/AIDS epidemic in sub-Saharan Africa has already orphaned a generation of children, and it is projected that by 2010, 18 million African children under the age of 18 are likely to be orphans from this single cause (UNICEF, 2005, The state of the Worlds Children: Childhood under threat. New York: UNICEF). Results from a Kellogg funded OVC project (Skinner et al., 2004, Definition of orphaned and vulnerable children. Cape Town: HSRC) supported the construct that the loss of either or both parents would indicate a situation of likely vulnerability of children. A key problem in the literature on the impact of orphanhood on the well-being of children, families and communities, is that the focus of assertions and predictions is often on the negative impact on 'AIDS orphans', or households. There are hardly any studies that compare the experiences of orphans with non-orphans. This paper thus attempts to fill that gap. It uses epidemiological data to explore the epidemiology of health and vulnerability of children within the context of AIDS in sub-Saharan Africa. Because of data limitations, only the following aspects are examined: (i) orphan status; (ii) household structure (in particular, grandparent headedness and female-headedness); (iii) illness of parents; (iv) poverty; and (v) access to services, especially schooling, health, social services. While recognizing the limitations of the analysis, data presented in this paper indicates that orphans in sub-Saharan Africa are more vulnerable than non-orphans. The authors conclude with some suggestions for policy makers and programme implementers, highlighting the importance of focusing on interventions that will have maximum impact on the health and well-being of children.