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Notes: Summary: In this article, we describe several novel genetic vaccination strategies designed to facilitate the development of different types of immune responses. These include: the consecutive use of DNA and fowlpoxvirus vectors in “prime-boost” strategies which induce greatly enhanced and sustained levels of both cell-mediated immunity and humoral immunity, including mucosal responses; ii) the co-expression of genes encoding cytokines and cell-surface receptors, and the use of immunogenic carrier molecules, for immune modulation and/or Improved targeting of vector-expressed vaccine antigens; acid iii) the expression of minimal immunogenic arnino acid sequences, particularly cytotoxic CD8+ T-cell determinants, in “polytope” vector vaccines. The capacity to modulate and enhance specific immune responses by the use of approaches such as these may underpin the development of vaccines against diseases for which no effective strategies are currently available.

Notes: Spatially resolved magneto-optical (MO) images of a (0.3 nm Co/1.2 nm Pt)15 multilayer film with perpendicular magnetic anisotropy have been obtained by Kerr microscopy. This material exhibits a major hysteresis loop with two-step magnetization reversal. The MO images display four possible "stable" magnetic states distinguished by four different intensities. This behavior is explained by the presence of two different magnetic phases each which has a stable magnetization state either parallel or antiparallel to the applied field, and which may reverse quasi-independently from one another. © 1999 American Institute of Physics.

Notes: The reestablishment of native shrubs is part of the mandate under which mining companies extract mineral resources in Wyoming and other western states. Post-mining shrub density and species mixtures have been topics debated by various mine reclamation stake holders. By law, coal-mined lands in Wyoming must now meet a post-mining shrub density of 1 shrub/m2 on 20% of the affected area. To better understand the long-term results of shrub reclamation methods, we measured shrub density by species in 14 pre-1985 seedings at eight mines in three geographic regions of Wyoming. The sites studied were selected as Atriplex canescens (Pursh) Nutt. (fourwing saltbush) and grass or as Artemisia tridentata Nutt. ssp. wyomingensis (Beetle and Young) (Wyoming big sagebrush), fourwing saltbush, and grass post-mining communities. Shrub density and composition varied by site but typically reflected the seed mixtures used. Seedings that used a diversity of shrub species generally had greater 1994 shrub densities. Seeding rates between 60 and 1000 shrub seeds/m2 had a positive, linear relationship with shrub density up to 0.6 shrubs/m2 when sagebrush was part of the shrub seed mixture. We conclude that the likelihood of meeting the shrub standard can be enhanced by seeding diverse shrub mixtures at high seeding rates.

Notes: Sinusoidal Stimulation of Cardiac Cells. Introduction: Cardiac tissue subjected to sinasoidal stimulus Is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed. Methods and Results: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo-Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD. Conclusion: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.

Notes: Abstract  Background: Atrial fibrillation (AFIB) is the most common complication following coronary artery bypass grafting (CABG). Despite three decades of recognition, efforts to reduce the high incidence reported (15%-30%) have been largely unsuccessful. Reasons for postoperative AFIB are likely multifactorial. As a result, we defined a multidrug prophylaxis based on agents known to be individually effective. This method was applied prospectively to a series of consecutive CABG patients with the goal of reducing the incidence of new-onset postoperative AFIB. Methods: Isolated CABG with cardiopulmonary bypass was performed on 517 consecutive patients. A rapid recovery protocol emphasizing AFIB multidrug prophylaxis was applied to all patients. All patients received 10 μ of triiodothyronine intraoperatively when the clamp on the aorta was released. Immediately following CABG, parenteral magnesium was administered to assure a serum magnesium 〉 2.2 mEq/dL. Thyroxine 200 μg was administered parenterally to all patients on postoperative days 1 and 2. Metoprolol (25 mg to 100 mg/day) was begun on all patients after extubation provided: heart rate 〉 85 beats/min and systolic blood pressure 〉 130 mmHg. Parenteral procainamide (12 mg/kg) loading dose, followed by a maintenance dose (2 mg/min), was used for patients who developed premature atrial contractions (〉 1/min), nonsustained supraventricular tachycardia, or any episodes of atrial fibrillation. All patients also received postoperative digitalization, steroids, and aggressive diuresis. Results: The 30-day operative mortality was 3.7%. The overall incidence of new-onset postoperative AFIB was 10.3% (53 patients). There was no major difference in operative mortality (7.5% vs 3.2%, p = 0.23), Parsonnet risk score, or intraoperative variables between AFIB patients and the non-AFIB patients. Patients presenting with a preoperative acute myocardial infarction (p 〈 0.05), left main stenosis ≥ 70% (p 〈 0.01), and advanced age ≥ 70 years (p 〈 0.05) were at increased risk of developing AFIB. The length of stay for patients with AFIB was 9.9 ± 9.6 days versus 5.9 ± 5.2 days (p 〈 0.001). Conclusion: Application of a multidrug prophylaxis can reduce postoperative AFIB to a low incidence. Identification of associated clinical features can help predict patients at risk for postoperative AFIB. Additional strategies to target postoperative AFIB may include treatment at the earliest recognition of atrial rhythm instability.

Notes: AbstractBackground and Aim The Asymptomatic Cardiac Ischemia Pilot is the first randomized trial where revascularization involved choice of either coronary bypass or angioplasty used in an early or a delayed symptom-driven approach. One-year outcomes were favorable (reduced recurrent ischemia and adverse outcomes) for an early revascularization strategy (within 4 weeks), compared with an early medical strategy when revascularization was delayed until symptom-driven. This ancillary study examined variables influencing outcomes after these 2 revascularization approaches (early vs. delayed until symptom-driven). Methods: Participants were clinically stable coronary disease patients with stress-induced and daily life ischemia who underwent revascvularization. Characteristics associated with clinical outcomes occurring within the year following revascularization were examined using Cox regression analysis. Results: A total of 262 patients received revascularization; 170 in the early approach and 92 in the delayed symptom-driven approach. Thirty-three patients had adverse outcomes (death, nonfatal myocardial infarction, or repeat revascularization) during l-year follow-up. The most important independent predictor of improved outcome during the follow-up year was attempted revascularization of 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:08860440:JOCS1:ges" location="ges.gif"/〉 66% of vessels with significant stenosis for the early (risk ratio [RR] 0.25, 95% confidence interval [CI] 0.09–0.67) and the delayed (RR 0.21, CI 0.08–0.58) approaches. Factors such as age, stress test results, and coronary angiographic findings did not predict clinical outcome. Conclusions: Our findings are important in the planning of a large trial with longer follow-up.

Notes: Abstract : Diffuse axonal injury is a primary feature of head traumaand is one of the most frequent causes of mortality and morbidity. Diffuseaxonal injury is microscopic in nature and difficult or impossible to detectwith imaging techniques. The objective of the present study was to determinewhether axonal injury in head trauma patients could be quantified by measuringlevels of CSF tau proteins. Tau proteins are structural microtubule bindingproteins primarily localized in the axonal compartment of neurons. Monoclonalantibodies recognizing the form of tau found in the CSF of head traumapatients were developed by differential CSF hybridoma screening using CSF fromhead trauma and control patients. Clones positive for head trauma CSF tauproteins were used to characterize this form of tau and for ELISA development.Using the developed ELISA, CSF tau levels were elevated 〉1,000-fold in headtrauma patients (mean, 1,519 ng/ml of CSF) when compared with patients withmultiple sclerosis (mean, 0.014 ng/ml of CSF ; p 〈 0.001), normalpressure hydrocephalus (nondetectable CSF tau), neurologic controls (mean,0.031 ng/ml of CSF ; p 〈 0.001), or nonneurologic controls(nondetectable CSF tau ; p 〈 0.001). In head trauma, a relationship between clinical improvement and decreased CSF tau levels was observed. These data suggest that CSF tau levels may prove a clinically useful assay for quantifying the axonal injury associated with head trauma and monitoring efficacy of neuroprotective agents. Affinity purification of CSF tau from head trauma patients indicated a uniform cleavage of ~ 18 kDa from all six tau isoforms, reducing their apparent molecular sizes to 30-50 kDa. These cleaved forms of CSF tau consisted of the interior portion of the tau sequence, including the microtubule binding domain, as judged by cyanogen bromide digestion. Consistent with these data, CSF cleaved tau bound taxolpolymerized microtubules, indicating a functionally intact microtubule binding domain. Furthermore, epitope mapping studies suggested that CSF cleaved tau proteins consist of the interior portion of the tau sequence with cleavage at both N and C terminals.

Notes: Magneto-optical Kerr effect measurements on a (0.3 nm Co/0.6 nm Pt)15 multilayer film with perpendicular magnetization showed Kerr rotation hysteresis loops that are very square, but asymmetric: on the descending major loop, while the magnetization decreases rapidly once the applied field approaches the coercive field, there is a long tail as saturation is approached. Modeling of this behavior was performed using a Preisach-based approach. To account for the known changes in magnetization behavior as a function of the number of bilayers, the Preisach density function was replaced by the sum of as many Gaussian distributions as there were bilayers in the material. The parameters of these Gaussian functions were systematically varied. The resulting model shows a good fit to both the experimental major loop and a first-order reversal curve. © 1999 American Institute of Physics.

Notes: Objective To study the effect of total body irradiation (14.4 Gray) in childhood and adolescence on ovarian and uterine characteristics, and to investigate the response to physiological sex steroid serum concentrations.Design All long term post-pubertal female survivors of total body irradiation who had been treated in paediatric centres in Scotland were identified. Their ovarian and uterine characteristics were studied.Setting Recruitment was from follow up oncology clinics.Sample Nine women were identified, eight of whom were assessed and five progressed to detailed investigation. A control population of 12 women treated for acute leukaemia, but not treated with total body irradiation, and five healthy women with no history of childhood malignancy were recruited as controls.Methods Ovarian function was determined by measurement of serum gonadotrophins and sex steroids. Uterine response to physiological sex steroid replacement was investigated in women with ovarian failure, and to endogenous sex steroid production in women with ovarian function by ultrasound scan. The physiological sex steroid replacement was achieved with transdermal oestradiol patches and self administered vaginal progesterone pessaries.Main outcome measures Determination of ovarian function and uterine response to physiological sex steroid serum concentrations.Results Six of eight women treated with total body irradiation had ovarian failure; preservation of function was seen in two girls treated pre-pubertally who had biochemical evidence of incipient ovarian failure. Four women with ovarian failure had reduced uterine volume, undetectable blood supply and absent endometrium at baseline assessment; after three months of physiological sex steroid replacement treatment uterine blood supply and endometrial response were not significantly different from controls; uterine volume improved but remained significantly smaller than controls and correlated with age at total body irradiation.Conclusions Ovarian failure after total body irradiation is common and risk relates to age at treatment. Physiological sex steroid replacement improved uterine measures and these women may benefit from assisted reproductive technology.