Highlights on Cerebral Arteriovenous Malformation Treatment Using Combined Embolization and Stereotactic Radiosurgery: Why Outcomes are Controversial?

Cerebral arteriovenous malformations (AVMs) are abnormal tangling between brain arteries and veins causing an arteriovenous shunt called nidus with an intervening network of vessels from the region of formation and spans through the brain. AVM effect is debilitating to the affected individual due to associated persistent intracerebral hemorrhage, resulting in significant occurrences of seizures and neurological damage. Recent innovative treatments involve a combination of embolization (Embo) procedures followed by stereotactic radiosurgery (SRS), designed to optimize less-invasive practice for the obliteration of the AVMs.

Accumulation of daunomycin and fluorescent dyes by drug-transporting Malpighian tubule cells of the tobacco hornworn, Manduca sexta.

Insect Malpighian tubules actively transport a variety of xenobiotics, and it has been proposed that P-glycoprotein (P-gp), or the multidrug transporter, is involved. To test this idea, we observed the interaction of known P-gp substrates with isolated, living Malpighian tubules from tobacco hornworm (Manduca sexta) larvae. Specifically, the fluorescent drugs daunomycin, rhodamine 123, acridine orange and Hoechst 33342 were applied to the basal side of tubules (proximal portion) in a well of fluid on a coverslip; the subsequent distribution of the drugs was monitored by laser scanning confocal microscopy.

A cross-national comparison of institutionalized tube-fed older persons: the influence of contrasting healthcare systems.

Objective: Different health care settings may influence the type of patients selected for long-term tube-feeding. Clinical characteristics of older, tube-fed institutionalized subjects living in Ontario, Canada were compared with those in the United States (US).

Design: A cross-sectional cohort study Setting: Nursing homes in the states of Mississippi, Texas, and Vermont (US) and chronic care facilities in Ontario.

Extracortical descending projections to the rat inferior colliculus.

Feedback controlling is an important element in the sensory processing in the auditory system. It has been long recognized that the inferior colliculus (IC) sends direct ascending projections to the medial geniculate body (MGB), but receives feedback regulation from the auditory cortex. In the present study we probed the shorter extracortical projections to the IC, including the direct descending pathway from the MGB.

DNA-based vaccination against hepatitis C virus (HCV): effect of expressing different forms of HCV E2 protein and use of CpG-optimized vectors in mice.

DNA-based immunization may be of prophylactic and therapeutic value for hepatitis C virus (HCV) infection. In efforts to improve the immunogenicity of a plasmid expressing the second envelope protein (E2) of HCV, we evaluated in mice the role of the antigen localization and demonstrated that membrane-bound and secreted forms induced higher titers of E2-specific antibodies, as well as earlier and higher seroconversion rates, than the intracellular form, but all three forms induced strong CTL. We also investigated whether E2-specific antibody responses could be enhanced by CpG optimization of the plasmid backbone and showed that removal of neutralizing CpG dinucleotides did not have a significant effect but addition of 64 immunostimulatory CpG motifs significantly enhanced anti-E2 titers.

The effect of qualitative vs. quantitative presentation of probability estimates on patient decision-making: a randomized trial.

Background: Given the greater uncertainty surrounding probability estimates associated with qualitative (use of words or phrases) descriptions, the use of quantitative (numerical) information to communicate the risks and benefits of therapies is recommended but the impact of its use in decision aids is unexplored.

Objective: Using stroke prevention in atrial fibrillation as an example, to compare the impact of quantitative vs. qualitative descriptions of probability risk estimates in decision aids on the clinical decision-making process.

Factors influencing the adoption of blood alternatives to minimize allogeneic transfusion: the perspective of eight Ontario hospitals.

Objective: To identify and describe the factors influencing the use and nonuse of blood-sparing methods such as preoperative autologous donation, acute normovolemic hemodilution, and the use of cell salvage devices, hemostatic agents and erythropoietin.

Design: An interview survey.

Setting: Eight Ontario hospitals.

Defining parkinsonism in the Canadian Study of Health and Aging.

This study sought an operational definition of parkinsonism in elderly people (n = 2,914) who underwent a clinical examination in the Canadian Study of Health and Aging (CSHA). Parkinsonism was defined as having two of the following features: (1) bradykinesia of face or limbs, (2) resting tremor, (3) rigidity, and (4) abnormality of gait and posture. The association of parkinsonism with other parkinsonian-related features (prior diagnosis of Parkinson's disease, use of drugs with extrapyramidal side effects, and use of antiparkinsonian medications) and variables not expected to be related to parkinsonism (stroke and Hachinski score > 5) was determined.

CpG motifs for optimization of DNA vaccines.

The immunogenicity of DNA vaccines is due in part to the presence of stimulatory CpG motifs, which may actually be essential to their function. CpG motifs are unmethylated cytosine-guanine dinucleotides within a certain flanking base context and such sequences are commonly found in bacterial but not mammalian DNA. It appears that through evolutionary adaptation, the vertebrate immune system developed the ability to recognize these sequences as a "danger signal" and respond by rapid activation of the innate immune system.

Immune-mediated destruction of transfected myocytes following DNA vaccination occurs via multiple mechanisms.

The delivery of antigenic proteins in the context of a DNA vaccine leads to the intracellular synthesis of antigen and the induction of both humoral and cellular immune responses. Subsequent to immune activation, any transfected cell expressing the immunogenic protein should, by the rules of immunology, become a legitimate target for removal by immune-mediated mechanisms. Herein, we have used an indirect assay of myocyte integrity following intra-muscular (i.

Norepinephrine acts via alpha(2) adrenergic receptors to suppress N-type calcium channels in dissociated rat median preoptic nucleus neurons.

The median preoptic (MnPO) nucleus, a key CNS site for hydromineral and cardiovascular homeostasis, receives a dense norepinephrine innervation from brainstem autonomic centers. Since norepinephrine is known to influence neuronal excitability by modulating calcium channel function, we applied whole cell patch clamp techniques to study calcium currents in 116 dissociated MnPO neurons, including 30 cells identified by a retrograde label as projecting to the hypothalamic paraventricular nucleus. Norepinephrine (3-50 microM) suppressed high-voltage-activated calcium currents (HVA I(Ca)) in 80% of cells, selectively blockable by yohimbine and mimicked by UK14,304 and clonidine.

Inhibitory specificity and potency of proSAAS-derived peptides toward proprotein convertase 1.

Prohormone convertase 1 (PC1), mediating the proteolytic processing of neural and endocrine precursors, is thought to be regulated by the neuroendocrine protein proSAAS. The PC1 inhibitory sequence is mostly confined within a 10-12-amino acid segment near the C terminus of the conserved human proSAAS and contains the critical KR(244) dibasic motif. Our results show that the decapeptide proSAAS-(235-244)( 235)VLGALLRVKR(244) is the most potent reversible competitive PC1-inhibitor (K(i) approximately 9 nm).

Anti-SLIP1-reactive proteins exist on human spermatozoa and are involved in zona pellucida binding.

Sulpholipid immobilizing protein 1 (SLIP1) is an evolutionarily conserved 68 kDa plasma membrane protein, present selectively in germ cells. We have previously shown that mouse sperm SLIP1 is involved in sperm-zona pellucida (ZP) binding. In this report, we extended our study to the human system.

Polymorphic phases of galactocerebrosides: spectroscopic evidence of lamellar crystalline structures.

Fourier transform infrared spectroscopy was applied to study the structural and thermal properties of bovine brain galactocerebroside (GalCer) containing amide linked non-hydroxylated or alpha-hydroxy fatty acids (NFA- and HFA-GalCer, respectively). Over the temperature range 0-90 degrees C, both GalCer displayed complex thermal transitions, characteristic of polymorphic phase behavior. Upon heating, aqueous dispersions of NFA- and HFA-GalCer exhibited high order-disorder transition temperatures near 80 and 72 degrees C, respectively.

The association between antiulcer medication and initiation of cobalamin replacement in older persons.

As chronic use of antiulcer medications might predispose older persons to cobalamin deficiency, we studied participants (> 65 years) in the clinical examination of the Canadian Study of Health and Aging to test the association between the use of an antiulcer medication (histamine-2 blocker or proton pump inhibitor) at baseline with initiation of cobalamin replacement during the 5 year follow-up period. Of 1054 eligible subjects, 125 (11.7%) were taking an antiulcer medication at baseline.

The use-dependent sodium channel blocker mexiletine is neuroprotective against global ischemic injury.

Mechanisms responsible for anoxic/ischemic cell death in mammalian CNS grey and white matter involve an increase in intracellular Ca2+, however the routes of Ca2+ entry appear to differ. In white matter, pathological Ca2+ influx largely occurs as a result of reversal of Na+-Ca2+ exchange, due to increased intracellular Na+ and membrane depolarization. Na+ channel blockade has therefore been logically and successfully employed to protect white matter from ischemic injury.

Issues of consensus and debate for economic evaluation in rheumatology.

We report initial attempts at developing standards for the conduct of economic evaluations in rheumatology. We surveyed 25 clinicians and economists with an interest in rheumatology regarding the design and reporting of economic evaluations, with particular reference to 4 clinical scenarios relating to treatment for rheumatoid arthritis, osteoarthritis, and osteoporosis. The results demonstrated widespread agreement on a number of methodological issues such as statement of funding source, perspective, discounting, and allowance for uncertainty.

Development and evaluation of a decision aid for patients with stage IV non-small cell lung cancer.

Although guidelines for treating stage IV non-small cell lung cancer suggest that the patient's values should be considered in decision-making, there are no practical tools available to assist them with their decision-making. OBJECTIVE: To develop and evaluate a decision aid that incorporates patient values. DESIGN AND SAMPLE: (1) Before/after evaluation with patients referred to a regional cancer centre.

The effects of an 'explicit' values clarification exercise in a woman's decision aid regarding postmenopausal hormone therapy.

OBJECTIVE: To evaluate the incremental effect of a graphic weigh-scale values clarification exercise to explicitly consider the personal importance of the benefits versus the risks in a woman's decision aid regarding postmenopausal hormone therapy. DESIGN: Randomized controlled trial. Intervention Decision aid including information on options, benefits and risks, and their probabilities either followed by: (1) a graphic weigh-scale values clarification exercise to explicitly consider the personal importance of each benefit and risk; or (2) a summary of the main benefits and risks to implicitly consider benefits versus the risks.

XIAP regulates Akt activity and caspase-3-dependent cleavage during cisplatin-induced apoptosis in human ovarian epithelial cancer cells.

Chemoresistance is a major hurdle for successful cancer therapy. Although multiple mechanisms have been implicated to be involved in cisplatin resistance, recent evidence has suggested that X-linked inhibitor of apoptosis protein (XIAP) may be a key determinant in chemosensitivity in ovarian cancer. Cell fate is determined by a balance between cell survival and apoptotic signaling.

The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase.

The Ku antigen (70- and 80-kDa subunits) is a regulatory subunit of DNA-dependent protein kinase (DNA-PK) that promotes the recruitment of the catalytic subunit of DNA-PK (DNA-PKcs) to DNA ends and to specific DNA sequences from which the kinase is activated. Ku and DNA-PKcs plays essential roles in double-stranded DNA break repair and V(D)J recombination and have been implicated in the regulation of specific gene transcription. In a yeast two-hybrid screen of a Jurkat T cell cDNA library, we have identified a specific interaction between the 70-kDa subunit of Ku heterodimer and the homeodomain of HOXC4, a homeodomain protein expressed in the hematopoietic system.

The potential of oligodeoxynucleotides as mucosal and parenteral adjuvants.

Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants in mice when delivered by parenteral (intramuscular, subcutaneous) and mucosal (intranasal, oral and intrarectal) routes. We have recently shown that with mucosal delivery non-CpG ODN can also have immunostimulatory properties which, in contrast to the Th1-bias characteristic of CpG ODN, are predominantly Th2-like. Herein, using hepatitis B surface antigen (HBsAg) and tetanus toxoid (TT) as model antigens in BALB/c mice, we have examined a number of different ODN (CpG, non-CpG, poly-T, poly-CG) to determine their effects on immune responses after mucosal (oral) and parenteral (IM) immunizations.

Optimization strategies for DNA vaccines.

DNA immunization is a relatively new vaccination strategy that involves the direct introduction into the host of plasmid DNA encoding the desired antigen. The DNA enters host cells and results in immune responses following in vivo expression of the antigen. Although DNA-based immunization works well in animal models for the induction of both humoral and cell-mediated immune responses, its success in humans has been limited.