Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions.

Caspase-11, a member of the murine caspase family, has been shown to be an upstream activator of caspase-1 in regulating cytokine maturation. We demonstrate here that in addition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion (MCAO), a mouse model of stroke. Recombinant procaspase-11 can autoprocess itself in vitro.

Prosthetic considerations with periodontal root resective therapy, Part 2. Hemisections.

When a root and the overlying anatomic crown are removed as a unit, this procedure is referred to as a hemisection. Hemisection of a maxillary or mandibular molar is often a means of retaining teeth needed for restorative abutments or occlusal support. This treatment can yield predictable results using proper diagnostic, endodontic, surgical, and prosthetic techniques.

Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment.

Nitric oxide, a product of nitric oxide synthase activity, relaxes vascular smooth muscle and elevates brain blood flow. We evaluated the importance of eNOS to cerebral blood flow augmentation after L-arginine infusion and increases in flow after eNOS upregulation in SV-129 mice. Blood flow was measured by laser-Doppler flowmetry before and after L-arginine infusion (450 mg/kg during a 15-minute period) or measured by 14C-iodoamphetamine indicator fractionation or 14C-iodoantipyrine tissue equilibration techniques.

DNA methyltransferase contributes to delayed ischemic brain injury.

DNA methylation is important for controlling the profile of gene expression and is catalyzed by DNA methyltransferase (MTase), an enzyme that is abundant in brain. Because significant DNA damage and alterations in gene expression develop as a consequence of cerebral ischemia, we measured MTase activity in vitro and DNA methylation in vivo after mild focal brain ischemia. After 30 min middle cerebral artery occlusion (MCAo) and reperfusion, MTase catalytic activity and the 190 kDa band on immunoblot did not change over time.

Prosthetic considerations with periodontal root resective therapy, Part 1: Root amputations.

Root resective periodontal therapy is a procedure used to retain teeth needed for restorative abutments or occlusal support. Contraindications of root resective therapy include fused roots and inadequate bony support around remaining roots. When these situations exist, extraction is necessary.

In vivo potentiostatic studies at the electrode tissue interface: filter properties of the monophasic action potential (Ag/AgCl) electrode in living rat heart.

The monophasic action potential (Franz) catheter is regarded as the criterion standard for high fidelity recording of a class of physiological signals. However, its signal modulation characteristics have never been reported. Broadband impedance spectroscopy was performed in perfused living rat heart in a three-electrode potentiostatic configuration to determine the filtering characteristics of the MAP and model Ag/AgCl electrode-tissue interfaces.

Evidence for apoptosis after intercerebral hemorrhage in rat striatum.

The overall hypothesis that cell death after intracerebral hemorrhage is mediated in part by apoptotic mechanisms was tested. Intracerebral hemorrhage was induced in rats using stereotactic infusions of 0.5 U of collagenase (1-microL volume) into the striatum.

Specialty choices, compensation, and career satisfaction of underrepresented minority faculty in academic medicine.

Purpose: Despite efforts to increase the numbers of underrepresented minorities (URMs), only 3.9% of medical school faculty are URMs. The authors compared the specialty choices, compensation, and career satisfaction of minority faculty with those of their majority counterparts to determine whether there were differences that might affect the recruitment and retention of minority faculty.

Cocaine activation discriminates dopaminergic projections by temporal response: an fMRI study in Rat.

We applied a sensitive new functional magnetic resonance imaging technique to identify the pattern and determinants of cocaine-induced brain activation in drug-naive rats. At doses greater than 0.1 mg/kg iv, cocaine produced robust activation throughout cortex with the largest magnitude increase in frontal neocortex.

The impact of leaving against medical advice on hospital resource utilization.

Objective: To assess the effect of hospital discharge against medical advice (AMA) on the interpretation of charges and length of stay attributable to alcoholism.

Design: Retrospective cohort. Three analytic strategies assessed the effect of having an alcohol-related diagnosis (ARD) on risk-adjusted utilization in multivariate regressions.

Intensive care unit use and mortality in the elderly.

Objective: To examine utilization and outcomes of intensive care unit (ICU) use for the elderly in the United States.

Design: We used 1992 data from the Health Care Financing Administration to examine ICU utilization and mortality by age and admission reason for hospitalizations of elderly Medicare beneficiaries.

Main Results: Use of the ICU was least likely for the oldest elderly overall (85+ years, 21.

Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels.

The P/Q type voltage-gated Ca2+ channels are involved in membrane excitability and Ca2+-dependent neurotransmitter release within the CNS. Mutations in the CacnalA gene encoding the alpha1A subunit of the P/Q type Ca2+ channel have recently been reported in tottering mice and a more severely affected allele, leaner. Here we show using in vivo cortical microdialysis that evoked increases of extracellular glutamate levels are markedly attenuated in both mutants upon KCl-induced depolarization compared with wild-type mice.

Care during menopause: comparison of a women's health practice and traditional care.

Despite the growth in primary care-based women's health centers, little is known about the characteristics of women's health patients and the quality of care provided in women's health centers versus traditional practices. Our objective was to compare a women's health practice and a general internal medicine practice on issues of care during menopause. A cross-sectional survey was administered simultaneously to patients aged 50-70 and their primary care physicians in a women's health practice and an affiliated general internal medicine practice.

High altitude headache. Lessons from headaches at sea level.

There is little known about high altitude headache, except that it is an important and serious problem that often heralds the onset of acute mountain sickness. We do know that the brain itself is an insensate organ except for its meninges which contain sensory axons projecting from the trigeminal nerve. These nerve fibers travel in proximity to meningeal blood vessels and constitute an important component of the trigeminovascular system.

Spinal cord ischemia. Development of a model in the mouse.

Background And Purpose: Spinal cord ischemia with resulting paraplegia is a devastating complication of thoracoabdominal aortic surgery. Experimental models of spinal cord ischemia have been developed in primate, dog, pig, rabbit, and rat with variable reproducibility, but none has been developed in mouse. Because genetically engineered mice have become important to examine the impact of specific genes in ischemic pathophysiology, we sought to develop a reproducible mouse model of spinal cord ischemia.

Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade.

Necrotic and apoptotic cell death both play a role mediating tissue injury following brain trauma. Caspase-1 (interleukin-1beta converting enzyme) is activated and oligonucleosomal DNA fragmentation is detected in traumatized brain tissue. Reduction of tissue injury and free radical production following brain trauma was achieved in a transgenic mouse expressing a dominant negative inhibitor of caspase-1 in the brain.

Identifying pre- and postoperative predictors of cost and length of stay for coronary artery bypass surgery.

Prior studies of resource use for coronary artery bypass graft (CABG) surgery have either focused on a limited number of hospitals or have used charges instead of costs. We used a large statewide database (n = 6791) to study predictors of cost and length of stay (LOS) for CABG surgery. We used linear regression to sequentially model (a) specific procedures performed, (b) preoperative patient characteristics, and (c) postoperative events to determine the relative impact of these 3 factors on resource use.

Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression.

The neurotrophins and the tyrosine kinase (Trk) B receptor may play a protective role in the pathophysiology of cerebral ischemia. In this study, the authors investigated whether reducing endogenous expression of TrkB-binding neurotrophins modifies the susceptibility to ischemic injury after 1-hour middle cerebral artery occlusion followed by 23 hours of reperfusion in a filament middle cerebral artery occlusion model. Mice lacking both alleles for neurotrophin-4 (nt4-/-) or deficient in a single allele for brain-derived neurotrophic factor (bdnf+/-) exhibited larger cerebral infarcts compared to wild-type inbred 129/SVjae mice (68% and 91%, respectively, compared to controls).

Perfusion weighted imaging during migraine: spontaneous visual aura and headache.

Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n = 6), 7 during the headache phase following visual aura (n = 3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly decreased (27% +/- 0.

MRI measurement of the temporal evolution of relative CMRO(2) during rat forepaw stimulation.

This study reports the first measurement of the relative cerebral metabolic rate of oxygen utilization (rCMRO(2)) during functional brain activation with sufficient temporal resolution to address the dynamics of blood oxygen level-dependent (BOLD) MRI signal. During rat forepaw stimulation, rCMRO(2) was determined in somatosensory cortex at 3-sec intervals, using a model of BOLD signal and measurements of the change in BOLD transverse relaxation rate, the resting state BOLD transverse relaxation rate, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Average percentage changes from 10 to 30 sec after onset of forepaw stimulation for rCBF, rCBV, rCMRO(2), and BOLD relaxation rate were 62 +/- 16, 17 +/- 2, 19 +/- 17, and -26 +/- 12, respectively.

MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia.

The MEK1 (MAP kinase/ERK kinase)/ERK (extracellular-signal-responsive kinase) pathway has been implicated in cell growth and differentiation [Seger, R. & Krebs, E. G.

A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice.

Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A(1) adenosine receptor. However, the role played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitations, we explored the consequences of deleting the A(2A) adenosine receptor on brain damage after transient focal ischemia.

Pressure ulcer development in the VA: characteristics of nursing homes providing best care.

This study identifies structural characteristics of VA nursing homes that are associated with the best patient outcomes. We evaluated risk-adjusted rates of pressure ulcer development in VA nursing homes and related these rates to facility size, staffing patterns, teaching nursing home status, and rural versus urban locale. Higher rates of pressure ulcer development were seen among urban teaching nursing homes and among nursing homes associated with both larger and smaller VA hospitals.

Pathobiology of ischaemic stroke: an integrated view.

Brain injury following transient or permanent focal cerebral ischaemia (stroke) develops from a complex series of pathophysiological events that evolve in time and space. In this article, the relevance of excitotoxicity, peri-infarct depolarizations, inflammation and apoptosis to delayed mechanisms of damage within the peri-infarct zone or ischaemic penumbra are discussed. While focusing on potentially new avenues of treatment, the issue of why many clinical stroke trials have so far proved disappointing is addressed.