Predictors of psychological distress in carers of people with amyotrophic lateral sclerosis: a longitudinal study

BACKGROUND: The majority of people providing informal care for people with amyotrophic lateral sclerosis (ALS) are spouses. This prospective study set out to examine changes in and predictors of psychological distress in spouse carers of people with ALS. METHOD: Fifty spouse carers of people with ALS underwent an initial interview and at least 21 underwent two further interviews, at median intervals of approximately 5-6 months. They rated the functional impact of their partner's ALS on everyday activities and everyday cognitive, emotional and behavioural changes that might have occurred in the person with ALS. They also rated their own social support and marital relationship, and completed measures of mood, burden and strain. The ALS Severity Scale was also completed for their partner with ALS. RESULTS: Over time, carers' psychological distress (a global measure combining mood, burden and strain) increased significantly. Initially carers' psychological distress was best predicted by the psychosocial impact of their spouse/partners' ALS, the extent to which their partner demonstrated emotional lability and how many other people were considered as dependents of the carer. Subsequently, carer distress was best predicted by an initial measure of negative social support and by their initial satisfaction with their social relationships. CONCLUSIONS: Despite the significant physical impairment associated with ALS, psychosocial factors appear important in determining short- and longer-term psychological well-being in carers of people with ALS and may help clinicians to predict which carers are likely to experience psychological difficulties as part of their caring role.     

Fine needle aspiration cytology of clear cell "sugar" tumor (PEComa) of the lung: report of a case

PEComa (clear cell "sugar" tumor) of the lung is a rare benign tumor of the lung probably arising from the perivascular epithelioid cells (PECs). We report a case of pulmonary PEComa arising from the periphery of the right lobe of a 64-year-old male. To our knowledge, this is the second case in the English literature diagnosed by fine needle aspiration biopsy. In this case report, the clinical, cytologic and immunohistochemical features clear cell "sugar" tumor of the lung are discussed and compared with the previously published literature. The differential diagnosis and methods for distinguishing the various clear cells lesions in the lung are discussed.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Transcranial direct current stimulation in refractory continuous spikes and waves during slow sleep: a controlled study

Cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability. The purpose of the study was to investigate whether cathodal tDCS could interrupt the continuous epileptiform activity. Five patients with focal, refractory continuous spikes and waves during slow sleep were recruited. Cathodal tDCS and sham stimulation were applied to the epileptic focus, before sleep (1 mA; 20 min). Cathodal tDCS did not reduce the spike-index in any of the patients.     

Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat

Previous studies have demonstrated that moderate hypothermia reduces histopathological damage and improves behavioral outcome after experimental traumatic brain injury (TBI). Further investigations have clarified the mechanisms underlying the beneficial effects of hypothermia by showing that cooling reduces multiple cell injury cascades. The purpose of this study was to determine whether hypothermia could also enhance endogenous reparative processes following TBI such as neurogenesis and the replacement of lost neurons. Male Sprague-Dawley rats underwent moderate fluid-percussion brain injury and then were randomized into normothermia (37°C) or hypothermia (33°C) treatment. Animals received injections of 5-bromo-2'-deoxyuridine (BrdU) to detect mitotic cells after brain injury. After 3 or 7 days, animals were perfusion-fixed and processed for immunocytochemistry and confocal analysis. Sections were stained for markers selective for cell proliferation (BrdU), neuroblasts and immature neurons (doublecortin), and mature neurons (NeuN) and then analyzed using non-biased stereology to quantify neurogenesis in the dentate gyrus (DG). At 7 days after TBI, both normothermic and hypothermic TBI animals demonstrated a significant increase in the number of BrdU-immunoreactive cells in the DG as compared to sham-operated controls. At 7 days post-injury, hypothermia animals had a greater number of BrdU (ipsilateral cortex) and doublecortin (ipsilateral and contralateral cortex) immunoreactive cells in the DG as compared to normothermia animals. Because adult neurogenesis following injury may be associated with enhanced functional recovery, these data demonstrate that therapeutic hypothermia sustains the increase in neurogenesis induced by TBI and this may be one of the mechanisms by which hypothermia promotes reparative strategies in the injured nervous system.     

Trace fear conditioning detects hypoxic-ischemic brain injury in neonatal mice

Trace fear conditioning is a well-established test for the assessment of learning deficits in rodents. The aim of this study was to determine whether hypoxia-ischemia (HI) on postnatal day 9 (P9) in mice prevents the acquisition and expression of cued and contextual fear learning in early adulthood. Brain injury was induced in mice on P9 by 30 min of HI. On P49 and P50, animals were tested for: (1) trace fear conditioning with a short delay (2 s) between a shock-paired tone plus light and shock, (2) trace fear conditioning with a longer delay (20 s) between a shock-paired tone and shock, and (3) trace fear conditioning with a 2-second delay between a shock-paired tone and shock with additional visual, olfactory and tactile contextual cues in the fear conditioning apparatus. Outcome was assessed as percent of time spent freezing during a 2-min test. Histological assessment of the hippocampus and amygdala was performed on P51 to determine the extent of HI injury. Both shock-paired tone plus light with a short delay and shock-paired tone with a short delay plus additional contextual cues enhanced tone-induced freezing behavior in a nonhandled control group, but not in the HI group. For trace fear conditioning with a 20-second delay between the tone and the shock, freezing behavior did not differ significantly between nonhandled control and HI animals. Dorsal hippocampal and amygdala volumes were smaller in the ischemic hemispheres of the HI mice that displayed impaired fear memory with shock-paired tone plus light. In summary, we have shown that trace fear conditioning is a sensitive method for detecting memory impairments in adolescent mice following mild HI injury during the neonatal period. Combining a discrete conditioned stimulus (shock-paired tone plus light) with a short trace delay was the most sensitive method for using the fear conditioning paradigm to detect mild HI damage to the hippocampus and amygdala.     

Assessment of Autism in Community Settings: Discrepancies in Classification

Review of 78 evaluations for 29 young children examined practices used in assessment of autism spectrum disorders in three settings: public schools, developmental disabilities eligibility determinations, and our hospital-based early childhood mental health program. While similar rates of classification of autism spectrum disorders were found across sites, the rate of agreement by different evaluators for individual children was only 45%. Further, most community evaluators did not follow best practice guidelines nor use autism diagnostic tools with established psychometric properties. In this sample of primarily Latino, Spanish-speaking children, most community evaluators did not document assessment of the child in their native language, nor address the impact of language in their assessments.     

Activation and cellular localization of the p38 and JNK MAPK pathways in rat crescentic glomerulonephritis

BACKGROUND: The p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) are intracellular signal transduction pathways involved in the production of inflammatory mediators. Little, however, is known about the contribution of these pathways to renal inflammation, nor the cell types in which these pathways are activated within normal and inflamed kidneys. The aim of this study was therefore to delineate the pattern and cellular localization of p38 and JNK activation in normal rat kidney and rat acute and chronic inflammatory renal disease. METHODS: Normal male Sprague-Dawley rats and groups of rats given accelerated anti-glomerular basement membrane (GBM) disease were killed at 3 hours, day 1, day 7, or day 28 and examined for p38 and JNK pathway activation by Western blotting and immunolocalization of the phosphorylated p38 (p-p38) and JNK (p-JNK) kinases. RESULTS: In terms of glomerular MAPK activation, Western blotting identified the presence of both p-p38 and p-JNK in normal glomeruli, localized by immunohistochemistry to podocytes and epithelial cells of Bowman's capsule. In anti-GBM disease, Western blotting showed that p38 activation peaked at 3 hours and remained elevated above normal throughout the disease time course. JNK activation (via the 54 kD isoform) likewise increased at 3 hours of anti-GBM disease and remained elevated throughout disease. At 3 hours, p-p38, but not p-JNK, was localized to neutrophils and glomerular endothelial cells. p-JNK was localized to glomerular endothelial cells at day 7. Macrophages, lymphocytes, activated podocytes, and myofibroblasts were positive for both p-p38 and p-JNK. In terms of tubular MAPK activation, Western blotting identified p38 and JNK activation in tubules of normal kidney. Immunostaining showed that most cortical tubules contained some p-p38 and p-JNK stained cells. There was a significant increase in tubular p38 activation at 3 hours of anti-GBM disease, followed by increased JNK activation of the 54 kD isoform from day 7 onward, and the 46 kD isoform at day 28. Immunostaining of diseased tissue localized p-p38 and p-JNK to virtually all cortical tubular cells. CONCLUSION: The p38 and JNK MAPK pathways are activated in glomeruli and tubules of normal kidney. In acute anti-GBM disease, there was an increase in p38 activation within glomerular endothelial cells and within infiltrating neutrophils, suggesting an important role for p38 MAPK in acute inflammation. In progressive anti-GBM disease, p38 and JNK activation in podocytes, glomerular endothelial cells, infiltrating macrophages, T cells, and myofibroblasts suggests that both the p38 and JNK MAPK pathways are important in chronic inflammation and fibrosis. Blockade of these pathways may therefore be potentially therapeutic in the treatment of acute and chronic renal inflammation.