Lithium neurotoxicity: the development of irreversible neurological impairment despite standard monitoring of serum lithium levels.

We report the case of a 44 year old man who presented with a two-month history of dysarthria, ataxia and leg weakness whilst on maintenance lithium for bipolar disorder. Examination revealed significant cerebellar and pyramidal dysfunction. Serum lithium was 1.5 mmol/l, a moderate elevation above his usual stable levels of 0.4-0.8 mmol/l. The patient's past history included hypertension and chronic renal impairment and the development of neurological symptoms coincided with the recent onset of heart failure. On cessation of lithium he partially recovered, the main residuum being persistent cerebellar ataxia. The case is an example of lithium neurotoxicity developing insidiously in the absence of an overt acute phase syndrome, and highlights the need for keen observation of the patient in the hope of preventing permanent deficits.     

Dementia care. Part 1: guidance and the assessment process

This article outlines recent guidance on dementia care and provides information on dementia, its different subtypes, the assessment process and the utility of cognitive screening tools. As dementia progresses a person may gradually lose their ability to make decisions for themselves. The Mental Capacity Act 2005 (MCA) is one of the most significant Acts to be passed in the United Kingdom, which protects people with dementia and stresses the need to advocate on behalf of this vulnerable group. The MCA is described in detail as practitioners working in the field of dementia care need to be aware of its clauses, as they are likely to require knowledge of it on a frequent basis. Dementia, delirium and depression are often mistaken for one another and useful ways to differentiate between the different conditions are given in addition to comprehensive advice about the management of people with dementia admitted to hospital with delirium.     

Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy

The immune response to cancer is critically determined by the way in which tumor cells die. As necrotic, stress-associated death can be associated with activation of antitumor immunity, whole tumor cell antigen loading strategies for dendritic cell (DC)-based vaccination have commonly used freeze-thaw "necrotic" lysates as an immunogenic source of tumor-associated antigens. In this study, the effect of such lysates on the ability of DCs to mature in response to well-established maturation stimuli was examined, and methods to enhance lysate-induced DC activation explored. Freeze-thaw lysates were prepared from murine tumor cell lines and their effects on bone marrow-derived DC maturation and function examined. Unmodified freeze-thaw tumor cell lysates inhibited the toll-like receptor-induced maturation and function of bone marrow-derived DCs, preventing up-regulation of CD40, CD86, and major histocompatibility complex class II, and reducing secretion of inflammatory cytokines [interleukin (IL)-12 p70, tumor necrosis factor-alpha, and IL-6]. Although IL-10 secretion was increased by lysate-pulsed DCs, this was not responsible for the observed suppression of IL-12. Although activation of the nuclear factor-kappaB pathway remained intact, the kinase activity of phosphorylated p38 mitogen-activated protein kinase was inhibited in lysate-pulsed DCs. Lysate-induced DC suppression was partially reversed in vitro by induction of tumor cell stress before lysis, and only DCs loaded with stressed lysates afforded protection against tumor challenge in vivo. These data suggest that ex vivo freeze-thaw of tumor cells does not effectively mimic in vivo immunogenic necrosis, and advocates careful characterization and optimization of tumor cell-derived vaccine sources for cancer immunotherapy.     

Hereditary nonpolyposis colorectal cancer (Lynch syndrome): molecular pathogenesis and clinical approaches to diagnosis and management for nurses

Hereditary nonpolyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is the most common form of hereditary colorectal cancer and is responsible for 2% to 4% of all colorectal cancers in the Western hemisphere. Generally characterized by early-onset colorectal carcinoma with a mean age of presentation of 40 to 45 years, it can also manifest with extracolonic adenocarcinomas and cancers of the endometrium, ovaries, stomach, pancreas, small intestine, hepatobiliary tract, upper uroepithelial tract, brain, and skin. HNPCC is autosomal dominant and carries an 80% lifetime risk of cancer development. This review addresses the molecular underpinnings of HNPCC while providing a concise approach to clinical detection, diagnosis, and management of patients who may or may not test positive for an HNPCC-causing mutation. Although applicable to any patient-care setting in which cancer may be observed, this review specifically addresses the role of nurses in detecting, diagnosing, and clinically managing HNPCC.