Defining cause of death in stroke patients: The Brain Attack Surveillance in Corpus Christi Project

Stroke mortality is an important national health statistic and represents a frequent endpoint for epidemiologic studies. Several methods have been used to determine cause of death after stroke, but their agreement and reliability are unknown. Two hundred consecutive deaths of transient ischemic attack or ischemic stroke patients were identified (January 2000-September 2001) from an ongoing population-based stroke surveillance study in Texas, The Brain Attack Surveillance in Corpus Christi Project. Two neurologists independently recorded the cause of death based on two methods: 1) determining the underlying cause of death as defined by the World Health Organization, and 2) determining whether the death was stroke related. Kappa statistics with 95% confidence intervals were calculated by comparing agreement between methods within reviewers and between reviewers within methods. Agreement between the two cause-of-death-determination methods for each neurologist was 0.41 (95% confidence interval (CI): 0.31, 0.51) and 0.47 (95% CI: 0.38, 0.58), respectively. Agreement between neurologists for the underlying-cause-of-death method was 0.46 (95% CI: 0.32, 0.60); for the stroke-related method, it was 0.63 (95% CI: 0.52, 0.75). Accurate, reliable determinations of cause of death after stroke/transient ischemic attack are not currently feasible. More research is needed to identify a reliable process for coding cause of death from stroke.     

Potential hazards of fenvalerate in massive pollution influence the apoptosis sensitivity

Fenvalerate (Fen), a synthetic pyrethroid insecticide, is widely used in agricultural, domestic and veterinary applications. Fen induces abnormal cell proliferation and apoptosis, which are linked to its hazardous effects. However, this view is controversial and the underlying molecular mechanisms remain elusive. In the present study, the effects of Fen on cadmium (Cd)‐induced apoptosis and the associated molecular mechanisms were investigated in human myeloid leukemia U937 cells. U937 cells were treated with 50 μm cadmium chloride (CdCl₂) with or without Fen pretreatment at 1–50 μm . Apoptosis was evaluated by externalization of phosphatidylserine on the plasma membrane. The expression levels of apoptosis‐related proteins, including Bcl‐2 family members were determined by western blot analysis. The results revealed that pretreatment with Fen at 20 μm for 12 hours significantly inhibited Cd‐induced apoptosis. Decreased expression of pro‐apoptotic Bcl‐2 family proteins (Noxa and Bid) and increased expression of anti‐apoptotic proteins (Bcl‐xL, Mcl‐1 and XIAP) were observed after combined treatment with Fen and CdCl₂. Phosphorylation of ERK and AKT was increased, while phosphorylation of JNK was decreased by the combined treatment, compared with CdCl₂ treatment alone. In conclusion, Fen decreased apoptotic sensitivity induced by Cd in U937 cells. This effect was associated with activation of ERK and AKT, suppression of JNK and changes in expression of Bcl‐2 family proteins and XIAP. The present findings suggest a potential influence of Fen on Cd toxicity via suppression of apoptosis. Fen decreased apoptotic sensitivity induced by Cd, and thus it may contribute carcinogenic risk and influence on cancer therapy.     

Kikuchi's disease associated with hemophagocytosis

We report the case of a 40 year-old Nepali man admitted to the hospital with a one month history of fever associated with swelling, pain, and redness on the right side of the neck. On examination, tender lymph nodes were palpated in the right posterior cervical triangle. Bone marrow aspiration and biopsy showed hemophagocytosis. Cervical lymph node biopsy showed the typical necrotizing lymphadenitis of Kikuchi's disease. The patient was given non-steroidal anti-inflammatory drugs (Naproxen 500 mg twice daily orally). After ten days, the fever and lymphadenopathy subsided and he was consequently discharged.     

Single‐walled carbon nanotube and graphene nanodelivery of gambogic acid increases its cytotoxicity in breast and pancreatic cancer cells

Graphene and single‐walled carbon nanotubes were used to deliver the natural low‐toxicity drug gambogic acid (GA) to breast and pancreatic cancer cells in vitro, and the effectiveness of this complex in suppressing cellular integrity was assessed. Cytotoxicity was assessed by measuring lactate dehydrogenase release, mitochondria dehydrogenase activity, mitochondrial membrane depolarization, DNA fragmentation, intracellular lipid content, and membrane permeability/caspase activity. The nanomaterials showed no toxicity at the concentrations used, and the antiproliferative effects of GA were significantly enhanced by nanodelivery. The results suggest that these complexes inhibit human breast and pancreatic cancer cells grown in vitro. This analysis represents a first step toward assessing their effectiveness in more complex, targeted, nanodelivery systems. Copyright © 2014 John Wiley & Sons, Ltd.     

Role of proinflammatory cytokines in the pathophysiology of osteoarthritis

Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.     

Rhabdomyolysis associated with Mycoplasma pneumoniae pneumonia

We report a case of rhabdomyolysis associated with Mycoplasma pneumoniae pneumonia in a 37-year-old Sri Lankan man who presented to the emergency department with complaints of feverishness, shortness of breath, cough, and generalised muscle pain. He had a serum creatinine kinase of 14 220 U/L, serum myoglobin of 1822 ng/mL, and serum creatinine of 195 μmol/L. His chest X-ray revealed bibasilar interstitial infiltrates. The antimycoplasma antibody titre was high. The patient was successfully treated with aggressive intravenous fluid replacement and azithromycin. The outcome was rapidly favourable, allowing us to discharge the patient 12 days after admission. On discharge, the serum creatinine kinase was 924 U/L and the creatinine was 126 μmol/L; the chest examination was unremarkable.