Early diagnosis of acute kidney injury in critically ill patients

Acute kidney injury (AKI) is a common and serious problem in critically ill patients. Tests currently used to detect AKI (i.e., serum creatinine, serum urea and various urinary indices) often result in delayed detection of injury--becoming abnormal at 48-72 h after the initial insult. This delayed detection translates into a potential missed opportunity for therapeutic interventions at a time when kidney damage may be limitable or reversible. This may also, in particular, account for the poor clinical outcomes commonly associated with AKI. The development of novel serum and urinary biomarkers capable of detecting AKI at an earlier phase of illness is therefore vital. This article will review the pitfalls of current conventional testing in kidney injury and discuss the emergence of novel biomarkers with the potential to revolutionize the field of critical care nephrology.     

Cost-effectiveness analysis of telemedicine to evaluate diabetic retinopathy in a prison population

OBJECTIVE: A cost-effectiveness analysis was conducted to investigate the clinical and economic impact of teleophthalmology in evaluating diabetic retinopathy in prison inmates with type 2 diabetes. RESEARCH DESIGN AND METHODS: Based on a hypothetical teleophthalmology system to evaluate diabetic retinopathy patients with type 2 diabetes in a prison care setting, a Markov decision model was developed with probability and cost data derived primarily from published epidemiological and outcome studies. A 40-year-old African-American man with type 2 diabetes was used as a reference case subject. The number of quality-adjusted life-years (QALYs) gained was used as the clinical outcome, and the cost in U.S. dollars from the year 2003 was used as the economic outcome. Teleophthalmology and nonteleophthalmology strategies were compared using an expected QALYs calculation and two types of sensitivity analyses: probabilistic and traditional n-way sensitivity analyses. RESULTS: The teleophthalmology strategy dominates in the cost-effectiveness analysis for the reference case subject: 16,514/18.73 dollars QALYs for teleophthalmology and 17,590/18.58 dollars QALYs for nonteleophthalmology. Ninety percent of the Monte Carlo simulations showed cost effectiveness (annual cost/QALYs < or = 50,000 dollars) in the teleophthalmology strategy based on an assumed inmate population. Teleophthalmology is the better strategy if the number of diabetic inmates in the prison community is >500. CONCLUSIONS: Our cost-effectiveness analysis demonstrates that teleophthalmology holds great promise to reduce the cost of inmate care and reduce blindness caused by diabetic retinopathy in type 2 diabetic patients.     

IMMUNOPATHOGENICITY AND ONCOGENICITY OF MURINE LEUKEMIA VIRUSES : I. Induction of Immunologic Disease and Lymphoma in (BALB/c x NZB)F1 Mice by Scripps Leukemia Virus

This report clearly demonstrates that a systemic lupus erythematosus (SLE)-like syndrome and lymphoma can be induced in immunologically normal (BALB/c x NZB)F₁ mice by infection of neonates with a murine leukemia virus (MuLV) (Scripps leukemia virus [SLV] 60A) isolated from NZB lymphoblasts. SLV 60A was titered in vitro (XC test) and administered to newborn and adult (BALB/c x NZB)F₁ mice over six log₁₀ dilutions. Propagation of MuLV in the newborn recipients was indicated by greatly elevated serum Mu gs-1 levels which were proportional to the dose of virus given. The SLE-like syndrome was characterized by antinuclear antibodies (ANA) and immune complex-type glomerulonephritis. ANA production was related to the dose of virus and reached the highest levels at 8–16 wk. The incidence of glomerulonephritis was also correlated with the dose of virus and reached nearly 50% in the animals given the highest virus dose. Both titers of ANA and incidence of glomerulonephritis were greater in females than in males, although the amounts of Mu gs-1 in sera of both sexes were equal. The incidence of direct Coombs' positivity was not significantly affected by inoculation of this virus. The incidence and time of onset of thymocytic lymphoma were linearly related to the amount of virus inoculated. High serum Mu gs-1 levels predicted lymphoma development and reflected increases in the amount of infectious virus in the spleen. No induction of tumors, autoimmunity, or high serum Mu gs-1 levels followed administration of SLV 60A to 6-wk old (BALB/c x NZB)F₁ mice or inactivated 60A or active AKR virus to newborns.     

Cerebral radiation necrosis: A review of the pathobiology,diagnosis and management considerations

Radiation therapy forms one of the building blocks of the multi-disciplinary management of patients with brain tumors. Improved survival following radiation therapy may come with a cost, including the potential complication of radiation necrosis. Radiation necrosis impacts the quality of life in cancer survivors, and it is essential to detect and effectively treat this entity as early as possible.Significant progress in neuro-radiology and molecular pathology facilitate more straightforward diagnosis and characterization of cerebral radiation necrosis. Several therapeutic interventions, both medical and surgical, may halt the progression of radiation necrosis and diminish or abrogate its clinical manifestations, but there are still no definitive guidelines to follow explicitly that guide treatment of radiation necrosis. We discuss the pathobiology, clinical features, diagnosis, available treatment modalities, and outcomes in the management of patients with intracranial radiation necrosis that follows radiation used to treat brain tumors.     

Lamotrigine in epilepsy,pregnancy and psychiatry – a drug for all seasons?

Lamotrigine has been demonstrated to be effective as both an antiepileptic drug and a mood stabiliser. For epilepsy it is less efficacious than valproate in primary generalised epilepsy, but it is comparable to some traditional drugs in partial epilepsy. In psychiatry it has significant advantages over other mood stabilisers for the treatment and prevention of depressive phases of bipolar illness, but not for the treatment of mania. It has a more benign adverse effect profile than older antiepileptic agents and is not a proven teratogen. Risk of adverse reactions is reduced by commencing treatment at a markedly reduced dose that is gradually increased.     

Recovery from severe frontotemporal dysfunction at 3 years after N-methyl-d-aspartic acid (NMDA) receptor antibody encephalitis

Encephalitis associated with antibodies against N-methyl-d-aspartic acid (NMDA) receptor is characterized by severe memory deficits, decreased consciousness, epileptic seizures and movement disorders and occurs most commonly in young women. Recovery is mostly good but little is known about the disease course in patients whose treatment has been delayed severely. We present a 16-year-old girl with a 36-month follow-up. A single course of methylprednisolone attenuated some symptoms but severe and incapacitating frontotemporal syndrome remained. Second-line treatment with rituximab was initiated 12 months after the onset of symptoms. A surprising recovery occurred 18 months after treatment and 30 months after onset. Recovery in NMDA receptor antibody-associated encephalitis can be severely delayed and does not have to be linear. Whether delayed therapy contributed to recovery in this patient cannot be answered with certainty. Spontaneous recovery independent of therapy is possible, as it has been observed previously as late as 3 years after onset. Although serum antibodies disappeared with recovery in this patient, previous cases have shown serum antibodies to be unreliable markers of disease activity. Second-line treatment, especially with substances as well tolerated as rituximab, should at least be considered in NMDA receptor encephalitis with persistent neuropsychiatric syndromes after first-line therapy.