Background and Purpose-Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Methods-DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with NationalInstitute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 g/kg, 90 g/kg, and 125 g/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days. Results-Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (Pϭ0.0012) were observed with desmoteplase (125 g/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 g/kg; Pϭ0.757) and 60.0% (125 g/kg; Pϭ0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (Pϭ0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion. Conclusions-Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 g/kg. (Stroke. 2005;36:66-73.)
Solid-state 13C magic angle spinning (MAS) NMR has been used to investigate detergent-solubilized photosynthetic reaction centers of Rhodobacter sphaeroides R26, selectively enriched in [4-13C]-tyrosine. The reaction centers were frozen, in the dark and while subject to intense illumination, and studied at temperatures between approximately 215 and approximately 260 K. The signal consists of at least seven narrow lines superimposed on a broad doublet. The chemical shift anisotropy is similar to that for crystalline tyrosine. The two narrowest resonances, corresponding to signals from individual tyrosines, are 28 +/- 5 Hz wide, comparable to what is observed for quaternary carbons in linearly elastic organic solids. The line width as well as the chemical shift of these signals is essentially independent of temperature. This provides strong evidence for an unusually ordered, well-shielded, and structurally, electrostatically, and thermodynamically stable interior of the protein complex without structural heterogeneities. As the temperature is lowered, additional signal from the labels develops and the natural abundance resonances from the detergent broaden, providing evidence for considerable flexibility at the exterior of the protein complex and in the detergent belt at the higher temperatures. In addition, the NMR provides evidence for an electrostatically uniform and neutral complex, since the total dispersion in isotropic shifts for the labels is < 5 ppm and corresponds to electron density variations of less than 0.03 electronic equivalents with respect to tyrosine in the solid state or in solution. When the sample is frozen while subject to intense illumination, a substantial part of the protein is brought into the charge-separated state P.+QA.-. At least three sharp resonances, including the narrowest lines, are substantially reduced in intensity. It is argued that this effect is caused by the electronic spin density associated with the oxidized primary donor P.+. These results strongly suggest that the environment of the special pair is extremely rigid and question the role of protein conformational distortions during the primary photoprocess.
Compared to conventional treatment, anthroposophic treatment of primary care patients with acute respiratory and ear symptoms had more favourable outcomes, lower antibiotic prescription rates, less adverse drug reactions, and higher patient satisfaction.
Homeopathy appeared to be at least as effective as conventional medical care in the treatment of patients with the three conditions studied.
This qualitative research examines gender differences in offenders'ability to negotiate a positive identity once the pejorative labels of criminal, prostitute, drug dealer, and incompetent parents have been imputed onto them. In-depth semi-structured focused interviews were conducted with a purposeful information-rich sample of eight male and eight female offenders. Content analysis reveals that males were much more adept than female offenders at juggling with conventional and street norms to justify and/or resist stigmatizing labels in order to construct a favorable identity. Appeal to such personal strengths as know-how, competence, loyalty, and a code of honor allowed male offenders to challenge the boundaries between conventional and delinquent worlds. Concomitantly such an appeal gave rise to a sense of efficacy perception and an optimistic explanatory style. In contrast, even though female offenders were able to justify the labels of drug dealer, prostitute, and thief by appeal to higher loyalties and reject that of insane, all their justifications collapsed when having to negotiate the identity of incompetent mother. Female offenders' negative internal attributions and deprivation of the normative center-motherhood resulted in apathy, anomie, and lack of confidence in their ability to do something worthwhile. Rehabilitation guidelines would build female offenders' personal strengths while redirecting those exhibited by male offenders into lawful enterprises.
Introduction Hyperthermia following a severe traumatic brain injury (TBI) is common, potentiates secondary injury, and worsens neurological outcome. Conventional fever treatment is often ineffective. An induced normothermia protocol, utilizing intravascular cooling, was used to assess the impact on fever incidence and intracranial pressure (ICP) in patients with severe TBI. Methods A comparative cohort study of 21 adult patients with severe TBI (GCS ≤ 8) treated with induced normothermia [36–36.5°C rectal probe setting; intravascular cooling catheter (CoolLine®, Alsius Corporation, Irvine, CA)] were matched by age, gender, and severity of injury to 21 historical control severe TBI patients treated with conventional fever control methods. ICP was measured via an external ventricular catheter and time duration for ICP > 25 mmHg was calculated for the initial 72-h monitoring period. Non-parametric rank tests were performed. Results Mean (±SD) or median [range] demographics did not differ between groups [total N = 42 (6 female, 36 male, age 36.4 ± 14.8 years and initial GCS 7 [3-8], median and range]. Fever burden in the first 3 days (time >38°C) in the induced normothermia versus control group was significantly less at 1.6% versus 10.6%, respectively (P = 0.03). Mean ICP for patients with induced normothermia versus control was 12.74 ± 4.0 and 16.37 ± 6.9 mmHg, respectively. Furthermore, percentage of time with ICP > 25 mmHg was significantly less in the induced normothermia group (P = 0.03). Conclusion Induced normothermia (fever prophylaxis via intravascular cooling catheter) is effective in reducing fever burden and may offer a means to attenuate secondary injury, as evidenced by a reduction in the intracranial hypertension burden.
Eleven female drug-court participants looked at current and past experiences to assess their program and envision future program innovations. From these women's perspective, the strongest component of drug court was being surrounded by staff dedicated to their progress and recovery. Graduated supervision and accurate drug testing were appreciated rather than resented when the participants were not humiliated and were treated with respect. Wraparound services, resources, and referral; treatment facilities that accepted children; and individualized treatment plans and therapy with offenders who are ex-addicts, and preferably females, allowed for greater involvement and active participation in recovery. Progressing through three phases, acquiring skills, a job, and visitation rights to see their children or regaining custody, increased these women's sense of self-efficacy perception and confidence in their ability to lead a drug-free, meaningful life. Findings show the importance of qualitative criteria in evaluating drug-court participants' progress and the process of recovery.
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