Interpreting inorganic compositional depth profiles to understand the rate-limiting step in vapor phase infiltration processes.

Vapor phase infiltration (VPI) is a post-polymerization modification technique that infuses inorganics into polymers to create organic-inorganic hybrid materials with new properties. Much is yet to be understood about the chemical kinetics underlying the VPI process. The aim of this study is to create a greater understanding of the process kinetics that govern the infiltration of trimethyl aluminum (TMA) and TiCl4 into PMMA to form inorganic-PMMA hybrid materials. To gain insight, this paper initially examines the predicted results for the spatiotemporal concentrations of inorganics computed from a recently posited reaction-diffusion model for VPI. This model provides insight on how the Damköhler number (reaction versus diffusion rates) and non-Fickian diffusional processes (hindering) that result from the material transforming from a polymer to a hybrid can affect the evolution of inorganic concentration depth profiles with time. Subsequently, experimental XPS depth profiles are collected for TMA and TiCl4 infiltrated PMMA films at 90 °C and 135 °C. The functional behavior of these depth profiles at varying infiltration times are qualitatively compared to various computed predictions and conclusions are drawn about the mechanisms of each of these processes. TMA infiltration into PMMA appears to transition from a diffusion-limited process at low temperatures (90 °C) to a reaction-limited process at high temperatures (135 °C) for the film thicknesses investigated here (200 nm). While TMA appears to fully infiltrate these 200 nm PMMA films within a few hours, TiCl4 infiltration into PMMA is considerably slower, with full saturation not occurring even after 2 days of precursor exposure. Infiltration at 90 °C is so slow that no clear conclusions about mechanism can be drawn; however, at 135 °C, the TiCl4 infiltration into PMMA is clearly a reaction-limited process, with TiCl4 permeating the entire thickness (at low concentrations) within only a few minutes, but inorganic loading continuously increasing in a uniform manner over a course of 2 days. Near-surface deviations from the uniform-loading expected for a reaction-limited process also suggest that diffusional hindering is high for TiCl4 infiltration into PMMA. These results demonstrate a new, ex situ analysis approach for investigating the rate-limiting process mechanisms for vapor phase infiltration.

Frequency and outcomes of aortocoronary dissection during percutaneous coronary intervention of chronic total occlusions: a case series and systematic review of the literature.

BACKGROUND: Aortocoronary dissection can complicate percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). METHODS: We retrospectively examined the frequency and outcomes of aortocoronary dissection among 336 consecutive CTO PCIs performed at our institution between 2005 and 2012 and performed a systematic review of the published literature. RESULTS: Aortocoronary dissection occurred in six patients (1.8%, 95% confidence intervals 0.7%, 3.8%). All aortocoronary dissections occurred in the right coronary artery (CTO target vessel in five patients and donor vessel in one patient). The baseline clinical characteristics of patients with and without aortocoronary dissection were similar. Compared to patients without, those with aortocoronary dissection were more likely to undergo crossing attempts using the retrograde approach (25% vs. 67%, P = 0.036) and experience a major complication (2.4% vs. 33.3%, P = 0.008). Technical and procedural success rates were similar in both groups. Of the six patients with aortocoronary dissection one underwent emergency coronary bypass graft surgery (CABG), four were treated with ostial stenting, and one was treated conservatively without subsequent adverse clinical outcomes. Systematic literature review provided 107 published cases of aortocoronary dissection during PCI, that occurred mainly in the right coronary artery (74.8%) and were treated with stenting (49.5%), emergency CABG (29%), or conservatively (21.5%). CONCLUSIONS: Aortocoronary dissection is an infrequent complication of CTO PCI and although it can be treated with stents in most patients, it may infrequently require emergency CABG.

Dealkylation of Poly(methyl methacrylate) by TiCl4 Vapor Phase Infiltration (VPI) and the Resulting Chemical and Thermophysical Properties of the Hybrid Material.

This study examines the chemical reaction pathways for vapor phase infiltration (VPI) of TiCl4 into poly(methyl methacrylate) (PMMA). VPI is a processing method that transforms organic polymers into organic-inorganic hybrid materials with new properties of interest for microelectronic patterning, technical textiles, and chemical separations. Understanding the fundamental chemical mechanisms of the VPI process is essential for establishing approaches to design the chemical structure and properties of these hybrid materials. While prior work has suggested that TiCl4 infiltration into PMMA does not disrupt the polymer's carbonyl bond, a clear reaction mechanism has yet to be proposed. Here, we present a detailed X-ray photoelectron spectroscopy study that presents evidence for a concerted reaction mechanism that involves TiCl4 coordinating with the PMMA's ester group to dealkylate the methyl side group, creating a chloromethane byproduct and primary chemical bonds between the organic and inorganic components of the hybrid material. Additional spectroscopy, quartz crystal microbalance gravimetry, and thermophysical and chemical property measurements of this material, including solubility studies and thermal expansion measurements, provide further evidence for this chemical reaction pathway and the subsequent creation of inorganic cross-links that network these TiOx-PMMA hybrid materials.

Cellulose Nanofibril Stabilized Pickering Emulsion Templated Aerogel with High Oil Absorption Capacity.

Nanocellulose-based aerogels, featuring a three-dimensional porous structure, are considered as a desirable green absorbent because of their exceptional absorption performance as well as the abundance and renewability of the raw material. However, these aerogels often require hydrophobic modification or carbonization, which is often environmentally harmful and energy-intensive. In this study, we introduce a Pickering-emulsion-templating approach to fabricate a cellulose nanofibril (CNF) aerogel with a hierarchical pore structure, allowing for high oil absorption capacity. n-Hexane-CNF oil-in-water Pickering emulsions are prepared as an emulsion template, which is further lyophilized to create a hollow microcapsule-based CNF (HM-CNF) aerogel with a density ranging from 1.3 to 6.1 mg/cm3 and a porosity of ≥99.6%. Scanning electron microscopy and Brunauer-Emmett-Teller analyses reveal the HM-CNF aerogel's hierarchical pore structure, originating from the CNF Pickering emulsion template, and also confirm the aerogel's very high surface area of 216.6 m2/g with an average pore diameter of 8.6 nm. Furthermore, the aerogel exhibits a maximum absorption capacity of 354 g/g and 166 g/g for chloroform and n-hexadecane, respectively, without requiring any surface modification or chemical treatment. These combined findings highlight the potential of the Pickering-emulsion-templated CNF aerogel as an environmentally sustainable and high-performance oil absorbent.

Correlation Between Maxillary Anterior Teeth and Common Facial Measurements.

Background: The symmetry between maxillary anterior teeth and the face holds significant importance. This study assessed and analyzed the relationship between facial parameters and anterior teeth in the maxillary arch of male and female subjects. Specifically, individual width and combined width (CW) measurements of the maxillary anterior teeth were investigated. Methods: This study involved a total of 150 dentate Yemeni subjects (74 men and 76 women), whose ages ranged from 18 years old to 30 years old. A maxillary cast was created, and two digital photographs of the face of each subject were taken and analyzed. Digital calipers and AutoCAD were used to gather measurement data of the dental parameters (intercanthal distance [ICD], interpupillary distance [IPD], interalar width [IAW], intercommissural width [ICW], and bizygomatic width [BZW]) and facial parameters (profile distance). Results: Significant correlations were found for the following: IPD and width of six maxillary anterior teeth of each of the study subjects; ICD and their central incisors; and BZW and their canine width measurements. In contrast, IAW and ICW were not correlated with all tooth measurements. Linear regression findings showed that the CW measurement of the four incisors was significantly correlated with all facial parameter measurements, excluding the ICW and IAW in females and the IAW, ICW, and profile distance in males. Conclusion: The IPD and ICD of males and females may be used to determine their CW measurements. The BZW and IPD of males can be used to take precise anthropological measurements of the width of the central canines and incisors. Meanwhile, the IPD distance of females can be used to assess the central and lateral incisor widths.

A sorbent containing pH-responsive chelating residues of aspartic and maleic acids for mitigation of toxic metal ions, cationic, and anionic dyes.

t-Butyl hydroperoxide-initiated cycloterpolymerization of diallylaminoaspartic acid hydrochloride [(CH2[double bond, length as m-dash]CHCH2)2NH+CH(CO2H)CH2CO2H Cl-] (I), maleic acid (HO2CH[double bond, length as m-dash]CHCO2H) (II) and cross-linker tetraallylhexane-1,6-diamine dihydrochloride [(CH2[double bond, length as m-dash]CHCH2)2NH+(CH2)6NH+ (CH2CH[double bond, length as m-dash]CH2)2 2Cl-] (III) afforded a new pH-responsive resin (IV), loaded with four CO2H and a chelating motif of NH+⋯CO2 - in each repeating unit. The removal of cationic methylene blue (MB) (3000 ppm) at pH 7.25 and Pb(ii) (200 ppm) at pH 6 by IV at 298, 313, and 328 K followed second-order kinetics with E a of 33.4 and 40.7 kJ mol-1, respectively. Both MB and Pb(ii) were removed fast, accounting for 97.7% removal of MB within 15 min at 313 K and 94% of Pb(ii) removal within 1 min. The super-adsorbent resin gave respective q max values of 2609 mg g-1 and 873 mg g-1 for MB and Pb(ii). IV was also found to trap anionic dyes; it removed 91% Eriochrome Black T (EBT) from its 50 ppm solutions at pH 2. The resin was found to be effective in reducing priority metal contaminants (like Cr, Hg, Pb) in industrial wastewater to sub-ppb levels. The synthesis of the recyclable resin can be easily scaled up from inexpensive starting materials. The resin has been found to be better than many recently reported sorbents.

Coronavirus disease 2019 and stroke in Iran: a case series and effects on stroke admissions.

OBJECTIVE: The coronavirus disease 2019 pandemic has affected healthcare systems around the globe and massively impacted patients with various non-infectious, life-threatening conditions. Stroke is a major neurological disease contributing to death and disability worldwide, and is still an ongoing issue during the pandemic. Here we investigate the impact of the coronavirus disease 2019 outbreak on stroke manifestations, treatment courses, the outcome of stroke patients, and the hospitalization rate in a referral center for stroke management in Tehran, Iran. METHODS: We extracted data regarding 31 stroke patients (10 patients with laboratory-confirmed coronavirus disease 2019) and compared the demographic and pathological characteristics of the patients with or without coronavirus disease 2019 infection. The association of demographic/pathological characteristics of stroke patients during the coronavirus disease 2019 pandemic and a corresponding period during the previous year (49 patients) and an earlier period during the same year as the pandemic (50 patients) was also evaluated. RESULTS: The absolute number of admissions decreased about 40% during the coronavirus disease 2019 pandemic. Except for the stroke severity (P = 0.002), there were no significant changes in the demographic and pathological characteristics of the stroke patients during the three studied periods. A significantly higher mean of age (75.60 ± 9.54 versus 60.86 ± 18.45; P = 0.007), a significant difference in the type of stroke (P = 0.046), and significantly higher stroke severity (P = 0.024) were observed in stroke patients with coronavirus disease 2019 compared with those of stroke patients without coronavirus disease 2019. Treatment approaches, duration of hospitalization, and mortality rates did not differ significantly. CONCLUSIONS: This report shows that the pandemic caused the number of acute stroke admissions to plummet compared to other periods. Although the pandemic did not affect the treatment plans and care of the patients, stroke cases with coronavirus disease 2019 had higher age, more large vessel ischemic stroke, and more severe stroke. Further studies are urgently needed to realize the probable interaction of the coronavirus disease 2019 pandemic and the neurologic disease.

New endpoint for ablation of ventricular tachycardia: change in QRS morphology with pacing at protected isthmus as index of isthmus block.

INTRODUCTION: Endpoints confirming block in the critical isthmus in sinus rhythm and with pace mapping have not been established. METHODS AND RESULTS: A 44-year-old man with a history of Tetralogy of Fallot presented with recurrent ventricular tachycardia (VT). Entrainment mapping was consistent with a macroreentrant circuit rotating in a clockwise fashion under the pulmonic valve. After termination of the VT in a critical isthmus located on the conal free wall, a pace map proximal to the site of successful ablation was consistent with a change in QRS morphology. This change in QRS morphology suggested critical isthmus block and successful ablation, which was confirmed by noninducibility with programmed stimulation. CONCLUSION: Evidence of conduction block can be used as an additional endpoint for successful ablation of VT.

Design and Synthesis of a Dual-Purpose Superadsorbent Containing a High Density of Chelating Motifs for the Fast Mitigation of Methylene Blue and Pb(II).

Maleic acid underwent alternate copolymerization with diallylaminomethylphosphonic acid·HCl [(CH2=CHCH2)2NH+CH2PO3H2 Cl-] and a cross-linker to give a new pH-responsive resin. Methylene blue (MB) removal from its 3000 ppm solution by the resin at pH 7 followed second-order kinetics with an E a of 34.8 kJ mol-1. MB removal was achieved very fast (10 min), attaining over 98.5% at 328 K. The q e obtained using MB concentrations in the range 100-8000 ppm fitted the Langmuir nonlinear isotherm model to give ΔG o, ΔH o, and ΔS o values of ≈ -21 kJ, 36.5 kJ mol-1, and 185 J mol-1 K-1, respectively. The resin is a superadsorbent with a q max value of 2445 mg g-1. The adsorbent also removed 97% Pb(II) within 5 min from its 10 000 ppb solution. The resin reduced the Pb(II) concentration from 200 to 3.8 ppb. The resin also demonstrated its ability to remove contaminants from industrial wastewater, reducing priority metal contaminants to ppb and sub-ppb levels. The resin can be recycled with stable efficiency. The outstanding performance places the resin in a top position in a list of recently reported sorbents.

Natural history of complications after intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Numerous trials of haemostatic and neuroprotective agents for intracerebral haemorrhage (ICH) have failed. We characterized the risk of complications after ICH in a trial-eligible patient population, to inform safety in future trials. METHODS: We used the Virtual International Stroke Trials Archive database to identify placebo-treated patients with spontaneous ICH, who were not comatose at admission, where randomization took place within 4 h of symptom onset, and where serious complication and outcome data were available. We described the complications encountered and assessed whether the absence of common complications influenced attainment of good functional outcome (mRS < or =4) at 90 days using logistic regression. RESULTS: Of 201 patients examined, 70.2% experienced at least one serious complication. Neurological complications occurred in 21%, infections amongst 11%, and thromboembolic complications in 2%. Extension of the haemorrhage occurred most frequently: its absence was a significant predictor of good functional outcome (P < 0.0001, adjusted OR for good functional outcome = 21.9, 95% CI: [5.5, 88.3]). Neither infection, nor cardiac, nor thromboembolic complications influenced functional outcome at 90 days. CONCLUSIONS: Three month outcome in ICH patients depends on initial stroke severity and on enlargement of the haemorrhage. Our results should inform safety in future clinical trials of putative ICH therapies.

Time for a Time Window Extension: Insights from Late Presenters in the ESCAPE Trial.

BACKGROUND AND PURPOSE: The safety and efficacy of endovascular therapy for large-artery stroke in the extended time window is not yet well-established. We performed a subgroup analysis on subjects enrolled within an extended time window in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial. MATERIALS AND METHODS: Fifty-nine of 315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial between 5.5 and 12 hours after last seen healthy (likely to have groin puncture administered 6 hours after that). Treatment effect sizes for all relevant outcomes (90-day mRS shift, mRS 0-2, mRS 0-1, and 24-hour NIHSS scores and intracerebral hemorrhage) were reported using unadjusted and adjusted analyses. RESULTS: There was no evidence of treatment heterogeneity between subjects in the early and late windows. Treatment effect favoring intervention was seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for mRS 0-2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%, P = .004) but no difference in symptomatic intracerebral hemorrhage. CONCLUSIONS: Patients with an extended time window could potentially benefit from endovascular treatment. Ongoing randomized controlled trials using imaging to identify late presenters with favorable brain physiology will help cement the paradigm of using time windows to select the population for acute imaging and imaging to select individual patients for therapy.

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2.

Cyclin-dependent kinase-5 (Cdk5) is required for neuronal survival, but its targets in the apoptotic pathways remain unknown. Here, we show that Cdk5 kinase activity prevents neuronal apoptosis through the upregulation of Bcl-2. Treatment of SH-SY5Y cells with retinoid acid (RA) and brain-derived neurotrophic factor (BDNF) generates differentiated neuron-like cells. DNA damage triggers apoptosis in the undifferentiated cells through mitochondrial pathway; however, RA/BDNF treatment results in Bcl-2 upregulation and inhibition of the mitochondrial pathway in the differentiated cells. RA/BDNF treatment activates Cdk5-mediated PI3K/Akt and ERK pathways. Inhibition of Cdk5 inhibits PI3K/Akt and ERK phosphorylation and Bcl-2 expression, and thus sensitizes the differentiated cells to DNA-damage. Inhibition of ERK, but not PI3K/Akt, abrogates Cdk5-medidated Bcl-2 upregulation and the protection of the differentiated cells. This study suggests that ERK-mediated Bcl-2 upregulation contributes to BDNF-induced Cdk5-mediated neuronal survival.

Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: A CT Perfusion Study.

BACKGROUND AND PURPOSE: Although blood pressure reduction has been postulated to result in a fall in cerebral perfusion pressure in patients with intracerebral hemorrhage, the latter is rarely measured. We assessed regional cerebral perfusion pressure in patients with intracerebral hemorrhage by using CT perfusion source data. MATERIALS AND METHODS: Patients with acute primary intracerebral hemorrhage were randomized to target systolic blood pressures of <150 mm Hg (n = 37) or <180 mm Hg (n = 36). Regional maps of cerebral blood flow, cerebral perfusion pressure, and cerebrovascular resistance were generated by using CT perfusion source data, obtained 2 hours after randomization. RESULTS: Perihematoma cerebral blood flow (38.7 ± 11.9 mL/100 g/min) was reduced relative to contralateral regions (44.1 ± 11.1 mL/100 g/min, P = .001), but cerebral perfusion pressure was not (14.4 ± 4.6 minutes(-1) versus 14.3 ± 4.8 minutes(-1), P = .93). Perihematoma cerebrovascular resistance (0.34 ± 0.11 g/mL) was higher than that in the contralateral region (0.30 ± 0.10 g/mL, P < .001). Ipsilateral and contralateral cerebral perfusion pressure in the external (15.0 ± 4.6 versus 15.6 ± 5.3 minutes(-1), P = .15) and internal (15.0 ± 4.8 versus 15.0 ± 4.8 minutes(-1), P = .90) borderzone regions were all similar. Borderzone cerebral perfusion pressure was similar to mean global cerebral perfusion pressure (14.7 ± 4.7 minutes(-1), P ≥ .29). Perihematoma cerebral perfusion pressure did not differ between blood pressure treatment groups (13.9 ± 5.5 minutes(-1) versus 14.8 ± 3.4 minutes(-1), P = .38) or vary with mean arterial pressure (r = -0.08, [-0.10, 0.05]). CONCLUSIONS: Perihematoma cerebral perfusion pressure is maintained despite increased cerebrovascular resistance and reduced cerebral blood flow. Aggressive antihypertensive therapy does not affect perihematoma or borderzone cerebral perfusion pressure. Maintenance of cerebral perfusion pressure provides physiologic support for the safety of blood pressure reduction in intracerebral hemorrhage.

Vasopressor administration during liver transplant surgery and its effect on endotracheal reintubation rate in the postoperative period: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: End-stage liver disease (ESLD) is associated with a low systemic vascular resistance due to peripheral vasodilatation. This phenomenon is aggravated by general anesthesia (GA) administered during liver transplantation, resulting in precipitous decreases in blood pressure. The excessive amounts (>3 mL/1 mL blood loss) of IV fluid administered to maintain hemodynamic stability during surgery promotes a fluid shift in the lung, which may lead to hypoxia in the immediate postoperative period. This pathophysiologic state may necessitate endotracheal reintubation and mechanical ventilation of the lungs, thus exposing the patient to a risk for morbidities related to laryngoscopy and endotracheal intubation, including deleterious cardiovascular responses to laryngoscopy, endotracheal damage due to laryngoscopic instrumentation, alteration in pulmonary mechanics secondary to controlled mechanical ventilation of the lungs, and delayed recovery associated with the sedation needed to perform these maneuvers. OBJECTIVE: The aim of this study was to determine whether the use of a vasopressor to antagonize the vasodilatory effect of GA would reduce the amount of IV fluids administered during liver transplantation, and whether the subsequent amelioration of fluid shift in the postoperative period would reduce the need for ventilatory support and endotracheal reintubation. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey. Patients aged > or =18 years scheduled to undergo orthotopic liver transplantation for ESLD were enrolled. The effect of use of an adjuvant vasopressor, together with controlled fluid administration (ie, the volume of IV fluid needed to maintain hemodynamic parameters at > or =80% of preoperative levels) (vasopressor group), was compared with that of fluid administration only (placebo group). We determined various postoperative outcome measures, primarily the amount of fluid administered and the need for endotracheal reintubation. RESULTS: Sixty-five patients were enrolled (44 men, 21 women; vasopressor, 33 patients; placebo, 32 patients). Sex distribution showed 19 men and 14 women in the vasopressor group and 25 men and 7 women in the placebo group (both, P < 0.05). The 2 treatment groups were statistically similar with regard to the rest of the baseline demographic and clinical characteristics and duration of surgery. The vasopressor group had a significantly lower prevalence of endotracheal reintubation compared with the placebo group (RR, 1:6; P < 0.05). The other postoperative parameters were statistically similar between the 2 groups. CONCLUSION: In this study of adults undergoing orthotopic liver transplantation for ESLD, use of an adjuvant vasopressor, together with controlled fluid administration, to maintain a stable hemodynamic status during GA reduced the need for endotracheal reintubation and its associated morbidities in the postoperative period compared with placebo.

Reliability of carotid doppler performed in a dedicated stroke prevention clinic.

INTRODUCTION: Doppler ultrasound (DUS) is used as a screening tool to assess internal carotid artery (ICA) disease. Recent reports suggest that the DUS may be inaccurate in over 28% of patients. We sought to evaluate the accuracy of DUS, when performed in a dedicated stroke prevention clinic (SPC). METHODS: We retrospectively reviewed the charts of patients who had a DUS performed in our SPC, followed by conventional cerebral angiography. Three groups of patients were defined. Group 1 had DUS measured ICA stenosis of >50%; Group II had a DUS measured ICA stenosis of <50%; Group III had complete ICA occlusion on DUS. RESULTS: Sixty-seven patients (69 arteries) were included in the study. There were 45 patients in Group I and based on the findings of cerebral angiography, carotid endarterectomy was considered inappropriate in only one patient--a misclassification rate of 2.2% (95% CI: 0 - 6.5%). Group II consisted of 19 patients and on cerebral angiography, none of these patients had a stenosis of >50%--a misclassification rate of 0%. Group III consisted of five patients in whom DUS showed complete ICA occlusion. The angiogram confirmed the occlusion in all five patients--a misclassification rate of 0%. Overall, misclassification rate was 1.45% (95% CI: 0 - 4.3%). CONCLUSIONS: Doppler ultrasound when performed in a stroke prevention clinic (SPC), has a high accuracy in measuring ICA stenosis of >50%. Doppler ultrasound is reliable in detecting complete ICA occlusion and finally DUS is a reliable screening tool to rule out clinically significant ICA stenosis.

Prevalence and treatment of "balloon-uncrossable" coronary chronic total occlusions.

BACKGROUND: The frequency and outcomes of "balloon-uncrossable" coronary chronic total occlusions (CTOs) have received limited study. METHODS: We retrospectively examined 373 consecutive CTO percutaneous coronary interventions (PCIs) performed at our institution between 2005 and 2013 to determine the frequency and treatment of balloon-uncrossable CTOs. RESULTS: Mean age was 63.7 ± 8.3 years and 98.9% of the patients were men. Twenty-four patients (6.4%, 95% confidence intervals 4.2% to 9.4%) were found to have a balloon-uncrossable CTO. Compared to the other CTO PCI patients, those with balloon-uncrossable CTOs had similar clinical and angiographic characteristics. Successful crossing of the balloon-uncrossable CTO was achieved in 22 of 24 patients (91.7%) using a variety of techniques, such as successive balloon inflations (43.5%), microcatheter advancement (21.7%), laser (8.7%), techniques that increase guide catheter support (13.0%), and subintimal lesion crossing (13.0%). Patients with balloon-uncrossable CTOs had longer procedure time (184.5 ± 77.9 vs 134.0 ± 69.0 min, P<.01), fluoroscopy time (55.2 ± 24.9 vs 37.9 ± 20.8 min, P<.01), and received high contrast volume (404.4 ± 137.9 vs 351.7 ± 138.5 mL, P=.08), but had similar incidence of major complications (8.3% vs 3.2%, P=.25) as compared with patients who did not have balloon-uncrossable CTOs. CONCLUSION: Balloon-uncrossable CTOs are encountered in 6.4% of contemporary CTO PCIs and can be successfully treated in most patients using a variety of techniques.

Inhibitory mechanisms in cerebral ischemia: a brief review.

Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of energy loss, excessive excitation promoting intracellular Ca2+ buildup, relative lack of inhibitory responses, generation of oxygen free radicals, especially during the reperfusion period and several other destructive cascades. Therapies aimed at decreasing the ill effects of glutamate are either not effective or have serious side-effects. Ca2+ entry blockers are generally not effective in cerebral ischemia, and data with protective effects of oxygen free radical scavengers in the post-ischemic period have shown conflicting results. There is recent interest with the use of agents that increase cerebral inhibitory responses after an ischemic insult. Such agents are effective when used before, during or up to 4 h after the ischemic insult. Many such medications have few side-effects and are in clinical use for other indications. This review will summarize inhibitory mechanisms that may be important in cerebral ischemia, and provide experimental evidence for their potential efficacy.

Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results.

BACKGROUND AND PURPOSE: A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study. METHODS: A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure. RESULTS: The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug. CONCLUSIONS: The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.

Vasopressin receptor expression and mutation analysis in corticotropin-secreting tumors.

Vasopressin is an important regulator of hypothalamo-pituitary-adrenal axis activation, primarily acting through the V3 receptor (V3R). Many patients with ACTH-secreting pituitary adenomas, but not normal individuals, respond to desmopressin, a relatively V2-specific vasopressin agonist, with increased ACTH and cortisol levels. We have searched for mutations of the V3R gene in ACTH-secreting pituitary adenomas and one ectopic ACTH-secreting tumor. No abnormalities were found in 12 tumors studied by PCR-single strand conformation polymorphism (PCR-SSCP) analysis. We then verified by RT-PCR whether the response to desmopressin was due to overexpression of the V3R or abnormal expression of the V2R in the pituitary tumor. We found that the V2R gene was expressed in a number of corticotroph tumors and in the ACTH-secreting ectopic tumor, and that the V3R gene appears to be overexpressed in these tumors. We conclude that V3R mutations are unlikely to be present in the ACTH-secreting tumors we examined, but that the V2R gene is expressed in the majority of the samples tested, and the V3R is expressed in all of these tumors. We speculate that the response to the desmopressin test observed in patients with Cushing's disease may be due to abnormal expression of V3R or V2R in ACTH-secreting tumors.