Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen.

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis (n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV (P = 0.01), OKT3 (P = 0.02), and PWM (P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points (P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis.NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.

A millikelvin all-fiber cavity optomechanical apparatus for merging with ultra-cold atoms in a hybrid quantum system.

We describe the construction of an apparatus designed to realize a hybrid quantum system comprised of a cryogenically cooled mechanical oscillator and ultra-cold 87Rb atoms coupled via light. The outstanding feature of our instrument is an in situ adjustable asymmetric all-fiber membrane-in-the-middle cavity located inside an ultra-high vacuum dilution refrigerator based cryostat. We show that Bose-Einstein condensates of N=2×106 atoms can be produced in less than 20 s and demonstrate a single photon optomechanical coupling strength of g0=2π×9 kHz employing a high-stress Si3N4 membrane with a mechanical quality factor Qm>107 at a cavity setup temperature of TMiM = 480 mK.

The role of mode match in fiber cavities.

We study and realize asymmetric fiber-based cavities with optimized mode match to achieve high reflectivity on resonance. This is especially important for mutually coupling two physical systems via light fields, e.g., in quantum hybrid systems. Our detailed theoretical and experimental analysis reveals that on resonance, the interference effect between the directly reflected non-modematched light and the light leaking back out of the cavity can lead to large unexpected losses due to the mode filtering of the incoupling fiber. Strong restrictions for the cavity design result out of this effect and we show that planar-concave cavities are clearly best suited. We validate our analytical model using numerical calculations and demonstrate an experimental realization of an asymmetric fiber Fabry-Pérot cavity with optimized parameters.

Temporal aspects of visual perception in demyelinative diseases.

The study aims to test whether impaired conduction velocities following optic neuritis (ON) serve as a limiting factor on various temporal, as compared to static, aspects of vision. Critical Flicker fusion frequency (CFFF), two motion perception tasks (object and number-from-motion extraction tasks), high and low contrast acuities, and visual evoked potentials (VEPs) were assessed in 23 ON patients. Strong correlations were found between the various dynamic visual function scores. Furthermore, regression models revealed that each of the dynamic visual functions significantly predicted VEP latencies. These findings were specific to patients' affected eyes and were not evident for static visual functions. Fellow eyes' VEP latencies were best predicted by the VEP latencies of the affected eyes. The similar impact of VEP latencies on various dynamic visual functions suggests conduction velocity to be the common limiting factor for temporal-related visual perceptual abilities. The specificity of these findings to the patients' affected eyes and to dynamic visual functions highlights the precision of dynamic visual functions for identifying demyelinative attack. Prolonged VEP latencies in the fellow eyes seem to stem from different patho-physiological processes. The hypothesis that inter-eye synchronization in conduction latencies is important to accomplish visual processing (binocular vision) is further discussed.

The role of automatic computer-aided surgical trajectory planning in improving the expected safety of stereotactic neurosurgery.

PURPOSE: Minimal invasion computer-assisted neurosurgical procedures with various tool insertions into the brain may carry hemorrhagic risks and neurological deficits. The goal of this study is to investigate the role of computer-based surgical trajectory planning tools in improving the potential safety of image-based stereotactic neurosurgery. METHODS: Multi-sequence MRI studies of eight patients who underwent image-guided neurosurgery were retrospectively processed to extract anatomical structures-head surface, ventricles, blood vessels, white matter fibers tractography, and fMRI data of motor, sensory, speech, and visual areas. An experienced neurosurgeon selected one target for each patient. Five neurosurgeons planned a surgical trajectory for each patient using three planning methods: (1) conventional; (2) visualization, in which scans are augmented with overlays of anatomical structures and functional areas; and (3) automatic, in which three surgical trajectories with the lowest expected risk score are automatically computed. For each surgeon, target, and method, we recorded the entry point and its surgical trajectory and computed its expected risk score and its minimum distance from the key structures. RESULTS: A total of 120 surgical trajectories were collected (5 surgeons, 8 targets, 3 methods). The surgical trajectories expected risk scores improved by 76% ([Formula: see text], two-sample student's t test); the average distance of a trajectory from nearby blood vessels increased by 1.6 mm ([Formula: see text]) from 0.6 to 2.2 mm (243%). The initial surgical trajectories were changed in 85% of the cases based on the expected risk score and the trajectory distance from blood vessels. CONCLUSIONS: Computer-based patient-specific preoperative planning of surgical trajectories that minimize the expected risk of vascular and neurological damage due to incorrect tool placement is a promising technique that yields consistent improvements.

Focal demyelinative damage and neighboring white matter integrity: an optic neuritis study.

BACKGROUND: Neuronal loss following damage is often greater than expected from the severity of injury to the nerve itself. The visual pathways, which comprise a well-defined system, and optic neuritis (ON), which is usually a discrete event, make a fine model to study this phenomenon. OBJECTIVE: Understand the effect of focal optic nerve demyelination on neighboring white matter. METHODS: Diffusion tensor imaging and probabilistic tractography were used to identify and characterize the optic tracts and radiations of 17 ON and matched controls. Data were correlated with retinal nerve fiber layer (RNFL) thickness. RESULTS: Patients' optic tracts exhibited reduced axial diffusivity, which correlated with RNFL thickness values. Patients' optic radiations demonstrated intact axial diffusivity but reduced fractional anisotropy and elevated radial diffusivity, which could be explained by intra-bundle lesions. No correlations were found between diffusivity measurements in patients' optic tracts and radiations; or between RNFL thickness and optic radiations' diffusivity. CONCLUSIONS: Following ON, chronic axonal loss develops distally in the optic tracts, demonstrating Wallerian degeneration. Degeneration did not proceed to the optic radiations, opposing anterograde trans-neuronal changes. DTI in ON provides fine in-vivo human model for studying histological abnormalities in normal appearing white matter, localized in close proximity to damaged bundle.

Optimal performance of an immersed membrane bioreactor equipped with a draft tube for domestic wastewater reclamation.

One of the options to prevent membrane fouling is to implement air lifting that can improve the cake removal from the membrane surface. This study presents the results of tests that were carried out at the Institutes for Desert Research, Kiryat Sde-Boker, Israel, and focused on the influence of hydrodynamic conditions on fouling in a pilot-scale immersed membrane bioreactor (IMBR) using a hollow fiber membrane module of ZW-10 (Zenon Environmental, Canada) under ambient conditions. In this system, the cross-flow velocities across the membrane surface were induced by one conical and four cylindrical draft-tubes. The relationship between the crossflow velocity and the aeration intensity, the influence of the crossflow on fouling rate under various hydrodynamic conditions were investigated and optimal operating conditions were obtained. Optimal operating conditions were reached during the long-term experiment period (70 days) for the treatment of domestic wastewater. The system was stable without external chemical cleaning. The results showed that the permeate was of high quality, and the removal of COD and BOD was 94.0% and 98.8%, respectively. The crossflow near the membrane surface reveals a major contribution for minimizing membrane fouling, and could offer guidelines for future design of similar systems.

A loss of fecundity in a population of mudsnails Hydrobia ventrosa caused by larval trematodes does not measurably affect host population equilibrium level.

Host snail demography and trematode parasitism were followed for one host generation in a shallow brackish lagoon of the western Baltic Sea. In addition, a laboratory experiment was simultaneously conducted to quantify the effects of parasitic infection on host fecundity. Hydrobia ventrosa of the cohort of 1996 had a maximum life-span of up to 2 years and reproduced between May and November of their second calendar year in 1997. Snails died after reproduction. The first trematode infections appeared in May 1997 when the snails started to mature. Total trematode prevalence peaked in summer and declined during winter to the lowest level in early spring 1998. Eight taxa of larval trematodes were found. Egg production of females with trematode infections was significantly reduced. Among females with pre-patent infections, about 20% were still able to produce eggs. Among females with patent infections merely 9% could lay eggs, compared to an average of about 51% in uninfected females. Taking into account a summer prevalence of about 25%, parasitic infections caused an overall reduction in egg production of the snail host population of about 15%. The reduction in host fecundity as a result of larval trematode infection did not measurably affect the population dynamics of H. ventrosa, because other environmental factors, especially winter severity and available food supply, were concluded to be much more relevant.

Immersed membrane bioreactor (IMBR) for treatment of combined domestic and dairy wastewater in an isolated farm.

In many regions dairy farms and milk processing industries discharge large quantities of their wastes to the surroundings posing serious environmental risks. This problem is mostly faced in small dairy farms and isolated communities lacking both central collection and conventional wastewater treatment systems. Dairy wastewater is characterized by high concentrations of organic matter, solids, nutrients, as well as fractions of dissolved inorganic pollutants, exceeding those levels considered typical for high strength domestic wastewaters. With the purpose of treating the combined dairy and domestic wastewater from a small dairy farm in the Negev Desert of Israel, the use of a recent emerging technology of Immersed Membrane BioReactor (IMBR) was evaluated over the course of 500 test hours, under a variety of wastewater feed quality conditions (during the test periods, the feed BOD5 ranged from 315 ppm up to 4,170 ppm). The overall performance of a pilot-scale Ultrafiltration (UF) IMBR process for a combined domestic and dairy wastewater was analyzed based on the Data Envelopment Analysis (DEA) method. The IMBR performance in terms of membrane performance (permeate flux, transmembrane pressure, and organic removal) and DEA model (Technical Efficiency) was acceptable. DEA is an empirically based methodology and the research approach has been found to be effective in the depiction and analysis for complex systems, where a large number of mutual interacting variables are involved.

Hybrid membrane systems for secondary effluent polishing for unrestricted reuse for agricultural irrigation.

Field experiments are in progress for secondary wastewater upgrading for unrestricted utilization for agricultural irrigation. The integrative approach of secondary effluent polishing is based on using a hybrid UltraFiltration (UF) and Reverse Osmosis (RO) membrane pilot system with a capacity of around 1 m3/hr. The UF effluent is used to feed the RO membranes. The RO permeate is subsequently applied for vegetable irrigation. Field results indicate the importance of the UF component in the removal of the organic matter and the pathogens that are still contained in the secondary effluent. Under specific conditions, when the dissolved solids content is relatively low, regarding sanitary and health aspects, the UF effluent can be applied for unrestricted irrigation. During the RO stage most nutrients are removed, allowing application of the effluent without jeopardizing the soil fertility and the aquifers. Preliminary economic assessment indicates that the extra cost for effluent polishing via the UF stage only is in the range of 5 to 15 US cents/m3. The extra cost for the RO stage is also assessed at 10 to 25 US cents/m3. The additional cost depends to a large extent on the quality of the incoming raw secondary effluent and local requirements of the command region.

Effects of repeated doses of intravenous immunoglobulin in myasthenia gravis.

The authors administered repeated courses of intravenous immunoglobulin (IVIg) to nine patients at the onset of an exacerbation of generalized myasthenia gravis (MG). Anticholinesterase medication (nine patients) and corticosteroid dosage (six patients) had been kept constant for a 2-month period. Six patients received two courses, two patients received three courses, and one patient received five courses. Twenty of 23 courses resulted in satisfactory improvement beginning 4.3 +/- 1.2 days after start of IVIg and becoming maximal 8.2 +/- 2.0 days, with sustained improvement lasting 106.6 +/- 49.1 days. Vital capacity increased from an average of 1845.1 +/- 489 cc to 2894 +/- 762 cc (p less than 0.01) at peak effect. Four of nine patients had a decrease in strength before improvement. There was no significant change in acetylcholine receptor antibody titers before or after therapy. Side effects were minimal. Of the three patients who had nonsatisfactory course, two responded well to additional IVIg. IVIg can produce repeated beneficial effects in patients with MG and may be useful as an adjunct in the management of MG.

High-dose intravenous immunoglobulin in the management of myasthenia gravis.

Intravenous immunoglobulin, 400 mg/kg, was administered daily for five days to 12 patients with exacerbation of generalized myasthenia gravis. Degree of weakness, duration of illness, use of prednisone, and history of thymectomy or thymoma did not affect the response to intravenous immunoglobulin. Eleven patients improved, beginning 3.6 +/- 2.7 (mean +/- SD) days after the start of treatment and becoming maximal in 8.6 +/- 4.6 days, with sustained improvement lasting 52 +/- 37 days. Vital capacity increased from 1748 +/- 510 to 2700 +/- 614 mL at peak effect. Decreases in strength occurred in four patients beginning on day 3.2 +/- 2.5, lasted 1.5 +/- 0.6 days, and were mild in three patients. Other effects were minimal. There was no significant change in acetylcholine receptor antibody titers, which were elevated in all patients. Immunoglobulin seemed to produce a more rapid improvement than corticosteroids and is recommended as an adjunct in the management of myasthenia gravis exacerbations.

Inhibition of natural killer cell activity by a soluble substance released by rat peritoneal cells.

We describe here a soluble substance released by nonadherent cells from the peritoneal cavity of W/Fu rats that markedly inhibits the activity of mouse, rat, and human natural killer (NK) cells. The NK-inhibiting substance (NK-IS) has low molecular weight (less than 1000), is heat resistant (100 degrees for 15 min), and is insensitive to nonspecific proteases. NK-IS is produced in the presence of indomethacin (1 to 10 micrograms/ml), suggesting it is not prostaglandin. The inhibitory effect was seen on unstimulated as well as on cells activated in vivo or in vitro by Corynebacterium parvum. The activity of cells mediated antibody-dependent cell cytotoxicity (K-cells) was also inhibited by NK-IS although to a lesser degree. In sharp contrast, the substance had little effect on lysis mediated by murine or human cytotoxic T-lymphocytes. Production of NK-IS from rat peritoneal cells was significantly greater than by spleen cells. since the peritoneal cavity is relatively deficient in base-line NK activity compared to spleen, these data suggest that NK-IS may play an in vivo role in the expression of NK cytotoxicity.

Augmentation of NK activity by Corynebacterium parvum fractions in vivo and in vitro.

Biochemically modified whole cell preparations and derived fractions of Corynebacterium parvum (C. parvum) were evaluated for the ability to augment natural killer cell cytoxicity in vivo and in vitro in rats. Unfractionated C. parvum enhanced peritoneal cell (Pc) NK activity in a dose dependent fashion. This activity appeared to be enriched in insoluble light residue material obtained from hot phenol water extraction. Enhancement of Pc cytotoxicity was significantly greater at all time points tested in rats injected with light residue when compared to rats injected with comparable amounts (by dry weight) of unfractionated organisms. In addition, pyridine extractable material and HCl modified preparations were capable of boosting Pc NK activity following intraperitoneal (I.P.) injection. Periodate treatment abrogated C. parvum's ability to boost Pc cytotoxicity and insoluble residue material obtained from pyridine extraction was likewise devoid of NK-enhancing properties. Culture of rat spleen cells overnight with unfractionated C. parvum, light residue and pyridine residue materials enhanced NK cytotoxicity whereas HCl and periodate modified whole cell preparations as well as phenol and pyridine extractable material were incapable of boosting cytotoxicity in vitro. In vitro augmentation by culturing with light residue was dependent on the presence of adherent cells in rat spleen cell populations. Pyridine extracts boost cytotoxicity in vivo and have no effect in vitro while the opposite is true of pyridine residue material suggesting different mechanisms of NK augmentation by C. parvum between in vitro and in vivo systems.

Recognition by human and rabbit sera of common antigens to leukemia blast cells, peripheral blood B-lymphocytes, and monocytes.

A human serum (obtained from a multiparous and multiple-transfused patient with chronic myelogenous leukemia) and a rabbit antiserum (obtained by immunization with papain extracts from a B-lymphoblastoid cell line) showed reactivity against antigenic specificities (different from HLA) expressed on peripheral blood B-lymphocytes, unmarked lymphocytes, and monocytes. These antigenic determinants were expressed on myeloblasts and lymphoblasts from patients with acute leukemia (during the active phase of their disease) and on B-lymphoblastoid cell lines and lymphocytes from patients with chronic lymphocytic leukemia. Purified peripheral blood T-lymphocytes, mitogen (phytohemagglutinin)-activated T-lymphocytes, and lymphoblasts (with T-cell characteristics) obtained from patients with acute lymphoblastic leukemia or established lymphoblastoid cell lines lacked these antigenic specificities. Absorption experiments indicate that the antigen(s) detected on normal mononuclear cell populations, leukemia cells, and B-lymphoblastoid cell lines were either identical or highly cross-reactive.