In vitro controllability of the MagScrew total artificial heart system

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.     

Biochemical and biological properties of Staphylococcal enterotoxin K

Staphylococcus aureus is an important human pathogen which is implicated in a wide variety of diseases. Major determinants of the virulence of this organism include extracellular virulence factors. Staphylococcal enterotoxins (SEs) are important causative agents in staphylococcal toxic shock syndrome and food poisoning. Our study identified a novel enterotoxin, SEK, and examined its biochemical and biological properties. SEK had a molecular weight of 26,000 and an experimentally determined pI of between 7.0 and 7.5. SEK was secreted by clinical isolates of S. aureus. We demonstrated that SEK had many of the biological activities associated with the SEs, including superantigenicity, pyrogenicity, the ability to enhance the lethal effect of endotoxin, and lethality in a rabbit model when administered by subcutaneous miniosmotic pump. Recombinant SEK was shown to stimulate human CD4(+) and CD8(+) T cells in a Vbeta-specific manner; T-cells bearing Vbeta 5.1, 5.2, and 6.7 were significantly stimulated to proliferate.     

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9–14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9–14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.     

Systemic Administration of Immunostimulatory DNA Sequences Mediates Reversible Inhibition of Th2 Responses in a Mouse Model of Asthma

This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals.     

Comparison of abilities of recombinant interleukin-1α and -β and noninflammatory IL-1β fragment 163–171 to upregulate C3b receptors (CR1) on human neutrophils and to enhance their phagocytic capacity

Both recombinant IL-1 and - caused an upregulation of C3b receptors (CR1) on human neutrophils and caused a receptor-mediated enhancement of phagocytosis of C3b·IgG-coated microspheres by these leukocytes. The and forms of the recombinant cytokine were of comparable potency regarding CR1 upregulation, although both generally had less than 25% of the potency of FMLP in this respect. Recombinant IL-1 was slightly more potent than the form of the cytokine regarding phagocytosis of opsonized microspheres and, again, both forms were less potent than FMLP in causing an enhancement of phagocytosis by neutrophils. The synthetic noninflammatory immunostimulatory nonapeptide corresponding to residues 163–171 of IL-1 was completely inert with respect to upregulation of CR1 on neutrophils and the enhancement of phagocytosis by these cells. Thus this domain in the intact IL-1 molecule apparently is not involved in CR1 upregulation and the ensuing enhancement in phagocytosis by neutrophils, although it is apparently important in the immunostimulatory activity regarding the proliferation of lymphocytes.     

MR properties of excised neural tissue following experimentally induced demyelination

Changes in the magnetic resonance (MR) parameters of demyelinated neural tissue were measured in vitro using an experimental animal model. A tellurium (Te) diet was applied to weanling rats to induce the demyelination process in the sciatic nerve. The quantitative MR parameters, such as T(1), T(2) relaxation time constants and magnetization transfer (MT) were measured each day after applying the Te diet (up to 7 days) and were found to be substantially different from those of normal nerves. An increase in the average T(1) and T(2) was observed along with a decrease in the MT ratio (MTR) and the quantitative MT parameter M(0B), which describes the semisolid pool of protons. Most of the MR parameters correlated very well with the myelin fraction of neural tissue evaluated by quantitative histopathology. The T(2) relaxation spectrum provided the most efficient quantitative assessment of changes in neural tissue microstructure and its analysis resulted in a powerful tool to distinguish the processes of demyelination and inflammation. In comparison, the MT measurements were less successful.     

Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen,but not by the LACK antigen,are protective against experimental Leishmania (Leishmania) amazonensis infection

Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-gamma) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-gamma and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-gamma and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis.     

Asthma pharmacotherapy and utilization by children in 3 managed care organizations. The Pediatric Asthma Care Patient Outcomes Research Team

BACKGROUND: Asthma is the most common chronic disease among children and the most frequent cause of hospitalization. Appropriate pharmacotherapy is a cornerstone of published national guidelines for the care of children with asthma. OBJECTIVE: The goal was to compare the baseline pharmacotherapy and health care utilization from 1996 to 1997 in children with asthma at managed care organizations (MCOs). METHODS: A common protocol was used to extract the study sample from 3 MCOs with automated claims and pharmacy databases. Children were selected if they were 3 to 15 years old as of June 1997 with 1 or more encounters (outpatient, emergency department visit, hospitalization) with an asthma diagnosis in the previous year. RESULTS: Of the 13,352 children studied, less than 40% were given controllers during the 12-month interval, with ranges of 15% to 77% by level of bronchodilator use, 31% to 44% by age, and 38% to 42% by MCO. Among children given 6 or more bronchodilators, controller dispensing ranged from 73% to 89% among the 3 MCOs. Variability was most evident for inhaled corticosteroids, for which dispensing ranged from 51% to 70%. Rates of asthma hospitalization and emergency department visits also differed among the MCOs, ranging from 21 to 37 per 1000 person-years and 37 to 142 per 1000 person-years, respectively. CONCLUSION: Five years after dissemination of national guidelines for care, the pattern of asthma therapy does not reflect guideline recommendations. Variation among health care organizations with respect to asthma therapy and utilization of health services exists. In addition, controller medications may not be used by all children who could benefit from them.     

On the ERN and the significance of errors

The error-related negativity (ERN) is an event-related brain potential observed when subjects commit errors. To examine whether the ERN is sensitive to the value of errors, the motivational significance of errors was manipulated in two experiments. In Experiment 1, low and high monetary value errors were compared to evaluate the effect of trial value on the ERN. In Experiment 2, subjects performed a flanker task both while their performance was being evaluated and during a control condition. Consistent with the notion that the error-detection system is sensitive to the significance of errors, the ERN was significantly larger on high-value trials in Experiment 1 and during evaluation in Experiment 2. There were no corresponding effects on the correct response negativity, and no behavioral differences between conditions were evident in either experiment. These results are discussed in terms of the functional role of the ERN in response monitoring.