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The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9  GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36  GeV/c^{2}, rejecting cross sections above 9.2×10^{-48}  cm at the 90% confidence level.

Biomaterials and negative pressure wound therapy (NPWT) are treatment modalities regularly used together to accelerate soft-tissue regeneration. This study evaluated the impact of the design and composition of commercially available collagen-based matrices on the observed vacuum pressure delivered under NPWT using a custom test apparatus. Specifically, testing compared the effect of the commercial products; ovine forestomach matrix (OFM), collagen/oxidized regenerated cellulose (collagen/ORC) and a collagen-based dressing (CWD) on the observed vacuum pressure. OFM resulted in an ∼50% reduction in the observed target vacuum pressure at 75 mmHg and 125 mmHg, however, this effect was mitigated to a ∼0% reduction when fenestrations were introduced into the matrix. Both collagen/ORC and CWD reduced the observed vacuum pressure at 125 mmHg (∼15% and ∼50%, respectively), and this was more dramatic when a lower vacuum pressure of 75 mmHg was delivered (∼20% and ∼75%, respectively). The reduced performance of the reconstituted collagen products is thought to result from the gelling properties of these products that may cause occlusion of the delivered vacuum to the wound bed. These findings highlight the importance of in vitro testing to establish the impact of adjunctive therapies on NPWT, where effective delivery of vacuum pressure is paramount to the efficacy of this therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RWFV, HC, SGD, IM, HJR and BCHM are shareholders of Aroa Biosurgery Limited (Auckland, New Zealand). RWFV, TK, NT, CGD, HC, SGD, SGD, HJR, IM, and BCHM are paid employees of Aroa Biosurgery Limited (Auckland, New Zealand). BCHM is listed as inventor on patent US8415159B2, owned by Aroa Biosurgery Limited., (Copyright © 2022 Aroa Biosurgery Limited, New Zealand. Published by Elsevier Ltd.. All rights reserved.)

Background: Postoperative complications associated with seroma formation resulting from surgical dead space continue to present a challenge in modern surgery. There is an unmet need for new technologies that address surgical dead space as well as prevent seroma formation and associated downstream postoperative complications., Methods: The novel implantable tissue apposition and drainage system ENIVO was developed and tested in a bilateral ovine external abdominal oblique (EAO) resection model of surgical dead space. The ENIVO system is a portable powered pump and wound interface featuring air-purged vacuum closure (APVC) that delivers a sustained level of vacuum pressure (80 and 100 mmHg) to the treatment site with an intermittent burst of sterile filtered air through the implanted wound interface. Seroma area, seroma volume, and drain migration were assessed at postoperative days 7 and 14, and all animals were euthanized at day 28 with gross assessment of treatment efficacy including the presence of residual seroma and tissue apposition., Results: The bilateral model created relatively uniform defects of ~120 cm 2 following excision of ~30 to 50 g of EAO muscle. Median seroma area of ENIVO-treated defects was statistically smaller than standard of care (SoC)-treated defects at days 7 and 14. Median seroma volume at 14 days was significantly reduced in ENIVO-treated defects relative to SoC-treated defects [1.3 (IQR 0.0-79.5) mL and 188.5 (IQR 27.6-342.9) mL, respectively]. At postoperative day 28, 40% (n = 4/10) of SoC defects showed a residual seroma, whereas in contrast, none of the ENIVO-treated defects showed signs of a residual seroma. Median tissue apposition scoring was higher in the ENIVO treatment group [3 (IQR 3-3)] compared with the SoC group [3 (IQR 0-3)]., Conclusions: The ENIVO system represents a new approach to dead space management and seroma prevention and was shown to outperform a SoC surgical drain in a challenging large defect model of surgical dead space management and seroma prevention., (© 2022, HMP Global. All rights reserved. Reproduction in whole or in part prohibited. Content may not be reproduced in any form without written permission. Rights, Permission, Reprint, and Translation information is available at www.hmpglobal.com.)

Knowing accurate saturated vapor pressures of explosives at ambient conditions is imperative to provide realistic boundaries on available vapor for ultra-trace detection. In quantifying vapor content emanating from low-volatility explosives, we observed discrepancies between the quantity of explosive expected based on literature vapor pressure values and the amount detected near ambient temperatures. Most vapor pressure measurements for low-volatility explosives, such as RDX (1,3,5-trinitro-1,3,5-triazinane) and HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane), have been made at temperatures far exceeding 25 °C and linear extrapolation of these higher temperature trends appears to underestimate vapor pressures near room temperature. Our goal was to measure vapor pressures as a function of temperature closer to ambient conditions. We used saturated RDX and HMX vapor sources at controlled temperatures to produce vapors that were then collected and analyzed via atmospheric flow tube-mass spectrometry (AFT-MS). The parts-per-quadrillion (ppq v ) sensitivity of AFT-MS enabled measurement of RDX vapor pressures at temperatures as low as 7 °C and HMX vapor pressures at temperatures as low as 40 °C for the first time. Furthermore, these vapor pressures were corroborated with analysis of vapor generated by nebulizing low concentration solutions of RDX and HMX. We report updated vapor pressure values for both RDX and HMX. Based on our measurements, the vapor pressure of RDX at 25 °C is 3 ± 1 × 10 -11 atm (i.e., 30 parts per trillion by volume, ppt v ), the vapor pressure of HMX is 1.0 ± 0.6 × 10 -14 atm (10 ppq v ) at 40 °C and, with extrapolation, HMX has a vapor pressure of 1.0 ± 0.6 × 10 -15 atm (1.0 ppq v ) at 25 °C.

Background: STAR (stochastic targeted) is a glycemic control model-based framework for critically ill neonates that has shown benefits in reducing hypoglycemia and hyperglycemia. STAR uses a stochastic matrix method to forecast future changes in a patient's insulin sensitivity and then applies this result to a physiological model to select an optimal insulin treatment. Nasogastric aspiration may be used as an indicator to suggest periods of care when enteral feed absorption is compromised, improving the performance of glycemic control. An analysis has been carried out to investigate the effect of poorly absorbed feeds on glycemic control., Method: Clinical data were collected from eight patients on insulin therapy and enteral feed, which included large or significantly milky aspirates. Patients had a median gestational age of 25 weeks and postnatal age of 5.5 days. Virtual patients were created using the NICING model, and insulin sensitivity (SI) profiles were fit. Alternative feed profiles were generated whereby enteral feed absorption was redistributed with time to account for poor feed absorption. The effect of poor feed absorption, as indicated by aspirates, is investigated., Results: The average percentage change of SI 4 h before a significant aspirate was 1.16%, and 1.49% in the 4 h following the aspirate. No distinct relationship was found between the fractional change in SI and the volume of the aspirate. Accounting for aspirates had a clinically negligible impact on glycemic control in virtual trials., Conclusion: Accounting for aspirates by manipulating enteral feed profiles had a minimal influence on both modeling and controlling glycemia in neonates. The impact of this method is clinically insignificant, suggesting that a population constant for the rate of glucose absorption in the gut adequately models feed absorption within the STAR framework., (© 2013 Diabetes Technology Society.)

We report the detection of pulsed gamma rays from the Crab pulsar at energies above 100 giga-electron volts (GeV) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) array of atmospheric Cherenkov telescopes. The detection cannot be explained on the basis of current pulsar models. The photon spectrum of pulsed emission between 100 mega-electron volts and 400 GeV is described by a broken power law that is statistically preferred over a power law with an exponential cutoff. It is unlikely that the observation can be explained by invoking curvature radiation as the origin of the observed gamma rays above 100 GeV. Our findings require that these gamma rays be produced more than 10 stellar radii from the neutron star.

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

Calcium puffs are local Ca(2+) release events that arise from a cluster of inositol 1,4,5-trisphosphate receptor channels (IP(3)Rs) and serve as a basic "building block" from which global Ca(2+) waves are generated. Important questions remain as to the number of IP(3)Rs that open during a puff, their spatial distribution within a cluster, and how much Ca(2+) current flows through each channel. The recent discovery of "trigger" events-small Ca(2+) signals that immediately precede puffs and are interpreted to arise through opening of single IP(3)R channels-now provides a useful yardstick by which to calibrate the Ca(2+) flux underlying puffs. Here, we describe a deterministic numerical model to simulate puffs and trigger events. Based on confocal linescan imaging in Xenopus oocytes, we simulated Ca(2+) release in two sequential stages; representing the trigger by the opening of a single IP(3)R in the center of a cluster for 12 ms, followed by the concerted opening of some number of IP(3)Rs for 19 ms, representing the rising phase of the puff. The diffusion of Ca(2+) and Ca(2+)-bound indicator dye were modeled in a three-dimensional cytosolic volume in the presence of immobile and mobile Ca(2+) buffers, and were used to predict the observed fluorescence signal after blurring by the microscope point-spread function. Optimal correspondence with experimental measurements of puff spatial width and puff/trigger amplitude ratio was obtained assuming that puffs arise from the synchronous opening of 25-35 IP(3)Rs, each carrying a Ca(2+) current of approximately 0.4 pA, with the channels distributed through a cluster 300-800 nm in diameter.

The liberation of calcium ions sequestered in the endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors/channels (IP(3)Rs) results in a spatiotemporal hierarchy of calcium signaling events that range from single-channel openings to local Ca(2+) puffs believed to arise from several to tens of clustered IP(3)Rs to global calcium waves. Using high-resolution confocal linescan imaging and a sensitive Ca(2+) indicator dye (fluo-4-dextran), we show that puffs are often preceded by small, transient Ca(2+) elevations that we christen "trigger events". The magnitude of triggers is consistent with their arising from the opening of a single IP(3) receptor/channel, and we propose that they initiate puffs by recruiting neighboring IP(3)Rs within the cluster by a regenerative process of Ca(2+)-induced Ca(2+) release. Puff amplitudes (fluorescence ratio change) are on average approximately 6 times greater than that of the triggers, suggesting that at least six IP(3)Rs may simultaneously be open during a puff. Trigger events have average durations of approximately 12 ms, as compared to 19 ms for the mean rise time of puffs, and their spatial extent is approximately 3 times smaller than puffs (respective widths at half peak amplitude 0.6 and 1.6 micro m). All these parameters were relatively independent of IP(3) concentration, although the proportion of puffs showing resolved triggers was greatest (approximately 80%) at low [IP(3)]. Because Ca(2+) puffs constitute the building blocks from which cellular IP(3)-mediated Ca(2+) signals are constructed, the events that initiate them are likely to be of fundamental importance for cell signaling. Moreover, the trigger events provide a useful yardstick by which to derive information regarding the number and spatial arrangement of IP(3)Rs within clusters.

Background: As part of a study on the effects of a fat-supplemented phenylalanine (phe)-free protein substitute on the fatty acid status of children with phenylketonuria (PKU), the adequacy of the diets of children aged 1-10 years for fat and essential fatty acids (EFA) was assessed., Methods: Subjects randomized in a 1 : 1 ratio to a phe-free protein substitute supplemented with EFA (test-treatment group) or a phe-free, fat-free protein substitute (control group) for 20 weeks. 3-day semi-weighed records of food intakes collected at the end of the study period., Results: Total fat and alpha-linolenic acid (alpha-LA) intakes were found to be poor in the control group (n = 19). Those in the test-treatment group (n = 24) had higher fat and EFA intakes (P < 0.05), bringing intakes closer to population norms. The youngest children (<5 years of age) in the control group appeared to be especially vulnerable to poor fat intakes because of the restricted diversity of their diets and, regardless of age, alpha-LA intakes by this group were poor compared with the non-PKU population., Conclusions: The quantity and quality of fat in the diets of children with PKU, in particular young children, should be given careful consideration in trying to optimize the ratio of linoleic acid: alpha-LA in their diets and in satisfying the requirements of this group for fat and alpha-LA.

We have used the auditory thalamocortical slice to characterize thalamocortical transmission in primary auditory cortex (ACx) of the juvenile mouse. "Minimal" stimulation was used to activate medial geniculate neurons during whole cell recordings from regular-spiking (RS cells; mostly pyramidal) and fast-spiking (FS, putative inhibitory) neurons in ACx layers 3 and 4. Excitatory postsynaptic potentials (EPSPs) were considered monosynaptic (thalamocortical) if they met three criteria: low onset latency variability (jitter), little change in latency with increased stimulus intensity, and little change in latency during a high-frequency tetanus. Thalamocortical EPSPs were reliable (probability of postsynaptic responses to stimulation was approximately 1.0) as well as temporally precise (low jitter). Both RS and FS neurons received thalamocortical input, but EPSPs in FS cells had faster rise times, shorter latencies to peak amplitude, and shorter durations than EPSPs in RS cells. Thalamocortical EPSPs depressed during repetitive stimulation at rates (2-300 Hz) consistent with thalamic spike rates in vivo, but at stimulation rates > or = 40 Hz, EPSPs also summed to activate N-methyl-D-aspartate receptors and trigger long-lasting polysynaptic activity. We conclude that thalamic inputs to excitatory and inhibitory neurons in ACx activate reliable and temporally precise monosynaptic EPSPs that in vivo may contribute to the precise timing of acoustic-evoked responses.

Auditory cortex contributes to the processing and perception of spectrotemporally complex stimuli. However, the mechanisms by which this is accomplished are not well understood. In this review, we examine evidence that single cortical neurons receive input covering much of the audible spectrum. We then propose an anatomical framework by which spectral information converges on single neurons in primary auditory cortex, via a combination of thalamocortical and intracortical "horizontal" pathways. By its nature, the framework confers sensitivity to specific, spectrotemporally complex stimuli. Finally, to address how spectral integration can be regulated, we show how one neuromodulator, acetylcholine, could act within the hypothesized framework to alter integration in single neurons. The results of these studies promote a cellular understanding of information processing in auditory cortex.

Objective: Alexithymia and posttraumatic stress disorder (PTSD) might share a neuroendocrine pattern characterized by increased urinary norepinephrine (N) and decreased cortisol (C) levels, resulting in a high N/C ratio, at least among male alcoholics. We aimed to explore if this association can also be found in other populations., Methods: Twenty-four-hour urine samples were obtained from 12 major depressive disorder (MDD) patients and 23 healthy controls (HC) and tested for N and free C. Participants completed the 20-item Toronto Alexithymia Scale (TAS) and the Symptom Check List (SCL)., Results: Controlling for depression, the neuroendocrine parameters did not differ between the MDD and HC participants nor between women and men. The TAS was not associated with N, C or the N/C ratio in the MDD and HC participants nor in females alone. However, in men, the N/C ratio correlated significantly with the TAS (r = .80)., Conclusions: Our preliminary findings indicate that alexithymia is associated with an increased noradrenergic activity and a decreased basal activity of the hypothalamic-pituitary-adrenal (HPA) axis among men. This gender difference may reflect divergent underlying neurobiological processes of alexithymia in men and women.

Background: Chlamydophila pneumoniae was frequently found in bronchial secretions of children with therapy-refractory bronchitis or pneumonia. It was studied, how the agent modifies the course of disease and what findings are associated with the infection., Patients and Methods: Bronchial secretions obtained at bronchoscopy of 428 children were studied for C. pneumoniae infection using polymerase chain reaction with enzyme immunoassay detection. Children tested negative and positive were compared for their clinical findings., Results: C. pneumoniae was found in 143 children (33 %). A C. pneumoniae infection has been found to be associated with a purulent bronchial inflammation (90/143 vs. 144/285, p = 0.02), a Streptococcus pneumoniae co-infection (13/143 vs. 6/285, p = 0.002) and a restrictive disturbance (11/51 vs. 8/93, p = 0.04). Purulent inflammation (Odds ratio 7.9; 95 % confidence interval [CI] 1.6-39.3), 2 co-infections (Odds ratio 14.3; 95 % CI 1.4-144.4) and co-infection with M. pneumoniae (4/4 versus 9/26, p = 0.03; Mantel Haentzel 3.0; 95 % CI 1.1-8.0) were identified as factors more often associated with a restrictive disturbance in children with bronchial C. pneumoniae infection. An adequate antibiotic therapy improved pulmonary function. No association was found for wheezing, eosinophil inflammation of the nasal mucosa, alpha-1 antitrypsin or immunoglobulin deficiency in serum, level of secretory IgA in bronchial mucus, pathological lung scintigram, gastro-esophageal reflux disease, sweat test and other co-infections., Conclusions: In children with therapy-refractory bronchitis or pneumonia bronchial C. pneumoniae infection was associated with a more severe disease in case of several, mostly bacterial co-infections. Adequate antibiotic therapy for C. pneumoniae infection has been demonstrated to improve pulmonary function.

Auditory cortex neurons integrate information over a broad range of sound frequencies, yet it is not known how such integration is accomplished at the cellular or systems levels. Whereas information about frequencies near a neuron's characteristic frequency is likely to be relayed to the neuron by lemniscal thalamocortical inputs from the ventral division of the medial geniculate nucleus, we recently proposed that information about frequencies spectrally distant from characteristic frequency is mainly relayed to the neuron via "horizontal" intracortical projections from neurons with spectrally-distant characteristic frequencies [J Neurophysiol 91 (2004) 2551]. Here we test this hypothesis by using current source density analysis to determine if characteristic frequency and spectrally-distant non-characteristic frequency stimuli preferentially activate thalamocortical and horizontal pathways, respectively, in rat auditory cortex. Characteristic frequency stimuli produced current source density profiles with prominent initial current sinks in layers 3 and 4--the termination zone of lemniscal inputs from medial geniculate nucleus. In contrast, stimuli three octaves below characteristic frequency produced initial current sinks mainly in the infragranular layers. Differences between current source density profiles were only apparent for initial current sinks; profiles for longer-latency current sinks evoked by characteristic frequency and non-characteristic frequency stimuli overlapped to a greater degree, likely due to shared mechanisms of intracortical processing or to longer-latency thalamocortical contributions (lemniscal and nonlemniscal). To identify current source density profiles produced by activation of lemniscal thalamocortical inputs alone, we utilized the mouse auditory thalamocortical slice preparation. Electrical stimulation of the medial geniculate nucleus in vitro produced major current sinks in cortical layers 3/4, and excitation spread horizontally from this point throughout primary auditory cortex to produce current sinks in multiple cortical layers. These data support the hypothesis that relay of thalamocortical information throughout auditory cortex via horizontal intracortical projections may be the basis of broad spectral integration in vivo.

Background: Assessment of high-risk drinking in the general population can be problematic: questionnaire-based instruments may carry the problem of random or systematic recall bias, and the effectiveness of screening of single biomarkers has been shown to be insufficient. In this article, we analyze the alcohol intake/biomarker relationship of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and erythrocyte mean corpuscular volume (MCV). Specific aims were (1) screening effectiveness comparison of GGT, CDT, and MCV in terms of sensitivity, specificity, and positive (PPVs) and negative predictive values (NPVs) and the effect of covariates on these measures; (2) the comparison of summary measures for the effectiveness of screening: the receiver characteristic curve (ROC) and the area under the ROC; and (3) to answer the question of which covariates effect which biomarkers and whether accounting for relevant covariates increases the prognostic value of biomarkers to levels that allow for application in the general population., Methods: In a representative cross-sectional health survey in northeast Germany with data collection from 1997 to 2001, 4310 men and women were asked for their recent alcohol consumption and smoking. Biomarkers were analyzed from blood samples. The effectiveness of screening of CDT, GGT, and MCV for high-risk drinking (men: >60 g/day, women: >40 g/day) was analyzed with PPV and ROC curve analysis., Results: For all three biomarkers, PPVs for high-risk drinking are very low (< 50%). There are some effects of covariates on screening effectiveness and on PPV, and knowledge of these covariates increases screening effectiveness, but no subgroup that had a combination of covariate levels and prevalence of high-risk drinking that led to a PPV > 50% could be found., Conclusions: : Accounting for covariates in the screening procedure does not lead to a sufficient increase in PPV. Screening effectiveness of laboratory markers CDT, GGT, and MCV is insufficient for their application as screening tools for high-risk alcohol drinking in the general population. This was found using self-reported alcohol consumption as an imperfect gold standard, which is a limitation of the study, although self-reports are the standard instrument in comparable epidemiologic studies., (Copyright 2004 Research Society on Alcoholism)

Objective: Biomarker distributions must be well known for use as screening tools for hazardous alcohol consumption in general populations. The aim of this study was to investigate characteristics of carbohydrate-deficient transferrin (CDT) and to compare it with gamma-glutamyltransferase (GGT) and erythrocyte mean corpuscular volume (MCV) in regard to distribution in the general population; the dose response relationship between alcohol consumption and biomarkers; and the effect of gender, age, body mass index (BMI) and smoking., Method: In a cross-sectional health survey in northeast Germany (1997-2001), a sample of 7,008 men and women aged 20-79 years was drawn, following stratification by age and gender. Of this sample, 4,310 subjects (2,193 women) took part in the study. Alcohol consumption was evaluated by self-reports with a beverage specific quantity-frequency method., Results: Biomarker distributions differ across age and gender. The distribution of drinkers and nondrinking subjects showed considerable overlap. The association of alcohol consumption to laboratory markers is weak in the general population: strongest for GGT, followed by CDT and MCV For CDT and MCV it is weaker in women than in men. We found increasing risk of all three elevated marker values with increasing alcohol consumption and significant effects of age, gender, smoking and body mass index on the alcohol-biomarker dose response curve., Conclusions: When biomarkers are used for screening, all confounding effects have to be taken into account and adjusted normal ranges must be used. CDT shows no overall advantage over GGT. Low correlation of biomarkers with alcohol consumption, their high variability and widely spread ranges in nondrinking subjects limit the usefulness of these markers in general population settings.

The effects of neonatal sympathectomy of donors or recipients on posttransplantation arterial pressure were investigated in spontaneously hypertensive rats (SHR) by renal transplantation experiments. Conscious mean arterial pressure (MAP) and renal vascular resistance were 136 +/- 1 mmHg and 15.5 +/- 1.2 mmHg x ml(-1) x min x g in sympathectomized SHR (n = 8) vs. 158 +/- 4 mmHg (P < 0.001) and 20.8 +/- 1.1 mmHg x ml(-1) x min x g (P < 0.05) in controls (n = 10). Seven weeks after transplantation of a kidney from neonatally sympathectomized SHR donors, MAP in SHR recipients (n = 10) was 20 mmHg lower than in controls transplanted with a kidney from hydralazine-treated SHR (n = 10) (P < 0.05) associated with reduced sodium sensitivity of MAP. Neonatal sympathectomy also lowered MAP in F1-hybrids (F1H; SHR x Wistar-Kyoto rats). Within 6 wk after transplantation, renal grafts from untreated SHR increased MAP by 20 mmHg in sympathectomized F1H (n = 10) and by 35 mmHg in sham-treated F1H (n = 8) (P < 0.05). Neonatal sympathectomy induces chronic changes in SHR kidney function leading to a MAP reduction even when extrarenal sympathetic tone is restored. Generalized reduction in sympathetic tone resets the kidney-fluid system to reduced MAP and blunts the extent of arterial pressure rise induced by an SHR kidney graft.

To facilitate an understanding of auditory thalamocortical mechanisms, we have developed a mouse brain-slice preparation with a functional connection between the ventral division of the medial geniculate (MGv) and the primary auditory cortex (ACx). Here we present the basic characteristics of the slice in terms of physiology (intracellular and extracellular recordings, including current source density analysis), pharmacology (including glutamate receptor involvement), and anatomy (gross anatomy, Nissl, parvalbumin immunocytochemistry, and tract tracing with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). Thalamocortical transmission in this preparation (the "primary" slice) involves both alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid/kainate and N-methyl-D-aspartate-type glutamate receptors that appear to mediate monosynaptic inputs to layers 3-4 of ACx. MGv stimulation also initiates disynaptic inhibitory postsynaptic potentials and longer-duration intracortical, polysynaptic activity. Important differences between responses elicited by MGv versus conventional columnar ("on-beam") stimulation emphasize the necessity of thalamic activation to infer thalamocortical mechanisms. We also introduce a second slice preparation, the "shell" slice, obtained from the brain region immediately ventral to the primary slice, that may contain a nonprimary thalamocortical pathway to temporal cortex. In the shell slice, stimulation of the thalamus or the region immediately ventral to it appears to produce fast activation of synapses in cortical layer 1 followed by robust intracortical polysynaptic activity. The layer 1 responses may result from orthodromic activation of nonprimary thalamocortical pathways; however, a plausible alternative could involve antidromic activation of corticotectal neurons and their layer 1 collaterals. The primary and shell slices will provide useful tools to investigate mechanisms of information processing in the ACx.

Background: Reinnervation occurs in many transplanted tissues and organs. Sympathetic reinnervation in rat kidney grafts was investigated., Methods: Rats were syngeneically transplanted with a kidney and bilaterally nephrectomized. Reinnervation was assessed by immunohistochemical staining for neuron-specific protein gene product 9.5 (PGP 9.5) and by tissue norepinephrine measurements in grafts removed 1.5 (n=6), 3 (n=7), 6 (n=8), and 9 (n=7) months after transplantation., Results: PGP 9.5-positive neural structures were significantly reduced in grafts removed 1.5 and 3 months after transplantation compared with native kidneys with slightly increased numbers at 6 and 9 months after transplantation. Median transplant norepinephrine concentrations remained at approximately 3% compared with native kidneys until 9 months after transplantation., Conclusions: In transplanted rat kidneys, some reinnervation occurs in the hilum within 9 months after transplantation. This is not accompanied by a significant recovery of norepinephrine concentration in renal tissue indicating persistent sympathetic denervation.

The dopamine (DA) neurons in the ventral tegmental area and medial substantia nigra (VTA/mSN) projecting to the limbic forebrain and prefrontal cortex have long been postulated to play a major role in cognitive and behavioral effects of stress. In this study, the effects of a chronic stressor (prolonged exposure to cold) on the spontaneous activity of DA neurons in the VTA/mSN were examined. Extracellular single-unit recordings of DA neurons were performed in rats following a 17-day continuous exposure to a cold (4 degrees C) environment. Compared to controls, cold-exposed rats displayed 64% fewer spontaneously active DA neurons. The average spike activity (average firing rate, average spikes fired in bursts) of the DA cells that remained active in the cold-exposed rats did not differ significantly from controls. However, a significantly larger proportion of those cells showed excessive burst activity, compared to the DA cell population in controls. These results show that chronic stress can lead to the cessation of spontaneous activity in a subpopulation of VTA/mSN DA cells. These changes may indicate that unlike acute stress, which can potently activate the mesolimbic/mesocortical DA systems, chronic stress leads to an adaptive reduction in the number of active DA cells, perhaps altering the response of these systems to subsequent stressors.

Stimulation of the medial geniculate body in an auditory thalamocortical slice elicits a short-latency current sink in the middle cortical layers, as would be expected following activation of thalamocortical relay neurons. However, corticothalamic neurons can have axon collaterals that project to the middle layers, thus, a middle-layer current sink could also result from antidromic activation of corticothalamic neurons and their axon collaterals. The likelihood of thalamic stimulation activating corticothalamic neurons would be reduced substantially if the corticothalamic pathway was not well preserved in the slice, and/or if the threshold for antidromic activation was significantly higher than for orthodromic activation. To determine the prevalence and threshold of antidromic activation, we recorded intracellularly from day 14-17 mouse brain slices containing infragranular cortical neurons while stimulating the medial geniculate or thalamocortical pathway. Antidromic spikes were confirmed by spike collision and characterized according to spike latency "jitter" and the ability to follow a high-frequency (100 Hz) stimulus train. The ability to follow a 100-Hz tetanus was a reliable indicator of antidromic activation, but both antidromic and orthodromic spikes could have low jitter. Thalamic stimulation produced antidromic activation in two of 69 infragranular cortical neurons (<3%), indicating the presence of antidromic activity, but implying a limited corticothalamic connection in the slice. Antidromic spikes in 13 additional neurons were obtained by stimulating axons in the thalamocortical pathway. The antidromic threshold averaged 214+/-40.6 microA (range 6-475 microA), over seven times the orthodromic threshold for medial geniculate-evoked responses in layer IV extracellular (28+/-5.4 microA) or intracellular (27+/-5.6 microA) recordings. We conclude that medial geniculate stimulation activates relatively few corticothalamic neurons. Conversely, low-intensity thalamic stimulation strongly activates thalamocortical neurons. Thus, at low-stimulus intensities, the auditory thalamocortical slice can be used to probe mechanisms of thalamocortical function with limited antidromic activation of corticothalamic neurons.

Disturbances in the serotonergic system are considered to be implicated in the pathophysiology of depressive disorders. The possible role of the neurotrophic factor S100 beta, which is suspected to regulate regeneration of serotonergic synapses, has not been investigated in depressive disorders. The S100 beta concentration in the cerebrospinal fluid was measured in 11 patients with the current diagnosis of mild or moderate depressive episodes (DSM-IV) and in 11 matched control patients. Using the t test for paired samples, the presence of a depressive episode was significantly associated with an elevation of the cerebrospinal fluid concentration of S100 beta (t = 2.6, d.f. = 10, p = 0.024). Replications of this finding in severely depressed patients are necessary to confirm the association between neurotrophic factor S100 beta and depressive disorders., (Copyright 2001 S. Karger AG, Basel)

Background: Glycation reactions of proteins and other compounds, depending on blood glucose concentrations, have a detrimental effect on health., Objective: The association of diet and other lifestyle factors with glycated hemoglobin (Hb A(1c)) values was examined in a nondiabetic population., Design: This was a cross-sectional study of 1773 middle-aged men and women. Mean Hb A(1c) values were calculated for categories of diet and lifestyle factors, and odds ratios (ORs) for the highest versus lowest tertiles of Hb A(1c) were determined and compared., Results: The OR of being in the highest Hb A(1c) tertile compared with the lowest increased with greater age [age 40-44 y compared with >60 y: men (OR: 2.86; 95% CI: 1.60, 5.20) and women: (6.11; 3.15, 12.30)] and greater obesity [body mass index (in kg/m(2)) >25 and waist-hip ratio >1.0 in men and >0.8 in women): men (2.80; 1.48, 5.45) and women (1.73; 1.15, 2.61)]. High energy and energy-adjusted saturated fat intakes were associated with increased risk of being in the highest tertile of Hb A(1c) [highest compared with lowest quintile: (1.53; 1.04, 2.26; P for trend = 0.013) and (1. 98; 1.33, 2.95; P for trend = 0.003), respectively]. No significant associations were observed for intakes of carbohydrates, protein, dietary fiber, or beta-carotene; however, some of the associations were nearly significant. Alcohol, vitamin C, and vitamin E intakes were inversely related to risk [highest compared with lowest quintile: (0.56; 0.38, 0.83; P for trend = 0.001), (0.50; 0.33, 0. 74; P for trend = 0.003), and (0.65; 0.43, 0.96; P for trend = 0. 036), respectively]., Conclusion: Hb A(1c) values might be modifiable by diet and other lifestyle factors.

The role of sympathetic reinnervation of kidney grafts for the development of renal post-transplantation hypertension was investigated. F1-hybrids (F1H) obtained from crossing spontaneously hypertensive (SHR) and Wistar-Kyoto rats were transplanted with an SHR kidney and bilaterally nephrectomized. Seven (n = 7) and 42 days after transplantation (n = 9), transplanted kidneys were removed and renal norepinephrine concentrations were determined. In addition, mean arterial pressure (MAP) was measured in conscious bilaterally nephrectomized recipients of an SHR (n = 9) or F1H kidney (n = 8) 6 weeks after transplantation. Renal norepinephrine concentrations (ng/g wet kidney weight) decreased dramatically from 348.3 +/- 31.7 ng/g before (n = 7) to 9.9 +/- 2.5 ng/g at 7 days and 6.5 +/- 1.1 ng/g at 42 days after transplantation, indicating that there was no substantial sympathetic reinnervation of the grafts throughout the observation period. Despite the lack of reinnervation of the grafts, recipients of an SHR kidney but not recipients of an F1H kidney developed post-transplantation hypertension (MAP 172 +/- 4 mmHg versus 124 +/- 3 mmHg P < 0.001) within 6 weeks after transplantation. We conclude that post-transplantation hypertension in recipients of an SHR kidney does not depend on sympathetic reinnervation of the graft.

Unlabelled: Bleeding complications during renal replacement therapies can be attributed to coagulation system and platelet function alterations in uremia, and the application of heparin in extracorporeal circulation. Small protein losses during hemofiltration are always described, however the high molecular weight of coagulation factors should significantly prevent their removal during hemofiltration. To exclude degradation of coagulation factors under conditions of spontaneous ultrafiltration, the hemofiltrate of 40 patients with acute renal failure (treated with continuous veno-venous hemofiltration, CVVH) was sampled from the filtrate line after 1 h from the beginning of treatment and in 5 patients also after 12 and 24 h. Samples were investigated with human factor deficient plasma (VII, X, XI, XII) from donors with a congenital deficiency and with human plasma depleted of factor V, VIII, IX, and protein S and C. Factor XIII was detected photometrically. Subsequently the presence of factor- XIII and -VII activity was investigated in plasma and hemofiltrate from 16 patients treated with intermittent hemofiltration before (plasma) and after (plasma, hemofiltrate) therapy. These patients also suffered from acute renal failure and needed renal replacement therapies. Quality control was carried out with a buffer solution (<1% activity in the assays according to recommended protocols)., Results: Factor-V, -VIII, -IX, -X, -XI, and -XII activity, and protein C and S could not be detected in the hemofiltrate from continuous hemofiltration. Factor-VII and -XIII activity was present in the hemofiltrate (mean activity in CVVH: 1.93% for factor VII and 6.9% for factor XIII, mean activity in intermittent hemofiltration: <1% for factor-VII and 7.3% for factor-XIII). Three were no significant differences (Student's t-test) in plasma activity before and after intermittent hemofiltration of factor VII (44 vs. 47%, p = 0.39) and factor XIII (44 vs. 52%, p = 0.24). The presence of factor-VII and -XIII activity in the hemofiltrate cannot influence plasma activities in intermittent hemofiltration. Rapid new synthesis and short half-life should neutralize these effects. Elimination of coagulation factor-XIII activity should be excluded by the next generation of highly permeable membranes and on-line hemodiafiltration.

Several pesticides used as herbicides, insecticides and fungicides are known to be endocrine disrupting chemicals (EDCs). In three pair-matched studies we found changes in sex hormone concentrations and T-lymphocytes in relation to acute and chronic pesticide exposure. After acute exposure, 1 day later the concentrations of testosterone and especially estradiol decreased. T4- and T8-lymphocytes slightly increased. Effects of chronic occupational pesticide exposure were expressed by a higher level of testosterone and a larger ratio of T4-/T8-lymphocytes in comparison to control persons. Concentrations of LH in exposed men were higher after exposure than before. We assume an inhibition of the aromatase system by testosterone metabolites. The studies show two effects with regard to the duration of exposure: a hormonal and immune suppression after acute exposure and an activation of both systems following chronic exposure.

The removal of amino acids during continuous renal replacement therapies induces clinical problems. Previous studies on animals have shown nephroprotective (glycine, alanine) or negative effects (lysine) on renal function in occurrence of acute renal failure. Disturbed metabolism in acute renal failure needs adequate parenteral nutrition. On the other hand, experience with continuous renal replacement therapies of metabolic crises in inborn errors of metabolism indicate a good control of disturbed amino acid metabolism. The aim of our study was to find amino acids, that might play an important role in the pathogenesis, prognosis and detection of acute renal failure and severe illness, so far only estimated by lactic acid. Thirty-three probes (serum and hemofiltrate) were taken from patients, suffering with acute renal failure caused by septic shock, severe pancreatitis and hepatorenal syndrome, one hour after the beginning of extracorporal circulation, the conditions of treatment were standardized. The material was deproteinized and studied by the amino acid analyzer LBK 4251 Apha Plus (Pharmacia, Stockholm, Sweden), while the lactic acid concentration was determined in a standard laboratory. Proline, glycine, alanine, methionine and histidine showed a close relationship to the lactic acid levels, but these amino acids were an essential part of parenteral nutrition. A statistical relationship was also established in (amino acids with amide groups) asparagine, glutamine, citrulline, cystathionine and phosphoethanolamine. The mean values of most of the amino acids were higher than normal, but standard deviations were increased. The presence of these amino acids in hemofiltrate and the good sieving coefficients could mean that the better prognosis of critically ill patients in continuous renal replacement therapies may also be due to continuous control of amino acid levels (especially with amide groups).

Serum levels of growth hormone (GH: arithmetic mean of three measurements eight hours apart), somatomedin C (SmC), alkaline phosphatase activity and the bone isoenzyme of alkaline phosphatase (as the liver/bone isoenzyme ratio) were measured in 26 patients with acromegaly (11 men and 15 women; mean age 45.5 [24-66] years), 18 in the active and eight in the nonactive phase of the disease. Activity was characterized by a raised (660 [330-1149] ng/ml), inactivity by a normal (186 [40-300] ng/ml) SmC concentration. All 18 patients with active acromegaly had an abnormally low liver/bone isoenzyme ratio (mean of 0.66 [0.01-1.28]). In seven of the eight patients with inactive acromegaly it was within normal limits. Thus measurement of bone alkaline phosphatase, which is significantly cheaper than that of SmC, is suitable for assessing activity.

Prophylactic immunization with the current standard vaccine failed to prevent an epidemic of type A influenza in a large boarding school. In one House 31 boys were given amantadine 100 mg daily at the start of the epidemic. None of these boys suffered influenza whereas 30 per cent of the rest of the school was confined to the sickbays. This experience with amantadine challenges the policy of routine prophylactic immunization against influenza.

We determined the serum total alkaline phosphatase as well as the alkaline phosphatase isoenzyme pattern in untreated and treated hyperthyreoses in the condition of euthyreosis and compared them with those of a healthy control group. The isoenzyme patterns, expressed as L/K quotient, ranged between 1.3 and 2.5 in the normal group and between 0.3 and 1.3 in the group with hyperthyreosis. The increase of the total alkaline phosphatase in hyperthyreosis was nearly exclusively conditioned by the increase of the activity of the osseous isoenzyme. The latter was increased already also then, when the total alkaline phosphatase had not transgressed the upper border of the normal. Depending on the functional condition of the thyroid gland the liver isoenzyme did not show any significant changes. In the course up to one year under thyrostatic therapy the increased activity of the osseous alkaline phosphatase decreased into the normal region as an expression of the very slowly repairing hyperthyreosis-conditioned disturbances of the osseous metabolism. An increase of the activity of the total alkaline phosphatase or of the osseous isoenzyme in the initial phase of a thyreostatic therapy of the sequel of an increase of the reactive activity of osteoblasts and must not lead to diagnostic and therapeutic uncertainties. By reason of the high sensitivity of the L/K quotient in hyperthyreoses (L/K at 95.5 % below 1.3) with a simultaneously high specifity of 89.5% the alkaline osseous phosphatase is to be discussed by all means as a helpful parameter of the peripheral function of the thyroid gland.

Clinical influenza attacked 304 out of 576 boys at a west country boarding school. Influenza A/ENG/333/80 (H(1)N(1)), a drift from A/USSR/92/77, was isolated from 14 out of 40 throat swabs. Pre-epidemic sera from 64 new boys showed that 54 already had antibodies to H(1)N(1) and 40 of them had antibodies to this novel variant. Nevertheless, when their serum was re-examined post-epidemically, 36 showed a rise in antibody, indicating that infection had occurred.One hundred and twenty-six junior boys were given amantadine and, of these, 22 (17.4 per cent) developed influenza, whereas 218 (57 per cent) of 382 boys who did not take amantadine had influenza. The immune status was known for 64 boys, 43 of whom were given amantadine. Only five (11.6 per cent) became clinically ill while taking the drug, whereas 10 (47.6 per cent) of the remaining 21 boys became ill. When their serum was re-examined, it was found that 20/43 of those taking amantadine and 5/21 of those not taking the drug had subclinical infection. The two groups were comparable in their pre-epidemic antibody status and all lived within the same environment during the outbreak.It is concluded that amantadine secured a reduction in clinical influenza without protecting significantly against subclinical infection, thus allowing subtype specific immunity to develop.

Well defined results can be obtained quickly by in vitro test concerning the preservation effect of the preserved dog's pancreas. Clinical and chemical parameters were received during the hypothermic perfusion respectively during the refrigerant storage. The in vitro function tests were carried out after the preservation by insulin and glucagon stimulation. The results showed that the A and B cells of the dog's pancreas are completely able to function after a preservation of 24 hours. Thereby a strong formation of edemas by releasing high enzyme activities is caused during the mechanical perfusion of the organs. The simple refrigerant storage of the pancreata therefore, is the more suitable preservation form for organ transplantations.

If anti-sera are combined with native whole blood by an in-vitro technique, immunocomplexes are formed. They are fixed to erythrocytes and can be made visible by a scanning electron microscope on blood smears especially pretreated.

The renal clearance of furosemide and tetraethylammonium (TEA) were compared in 10 patients with hypertensive nephropathy. BUN and creatinine ranges were 10 to 88 mg/dl and 0.9 to 3.8 mg/dl, respectively. Diuretics were discontinued 48 hr prior to the study, and 2 consecutive clearances (ml/min/1.73 m2BSA) of creatinine were performed. The patient then received a bolus followed by a constant infusion of furosemide-14C and tetraethylammonium-14C (analyzed by specific methodology for plasma and urine), both in subpharmacologic doses. After 40-min equilibration sequential 20-min clearance periods were obtained. Both the clearance of furosemide (range 17 to 133) and TEA (range 99 to 443) correlated negatively with BUN and serum creatinine and positively with creatinine and urea clearances. Thus, by using a constant-infusion technique we demonstrated that the renal clearance of furosemide is depressed by azotemia in man and that there was greater depression with furosemide than with TEA.

The clearance of furosemide (F), whose renal tubular transport shares the classical characteristics of the organic acid system, was determined in dogs with varying degrees of azotemia and compared with tetraethylammonium (TEA), an organic base. Two normal and eight azotemic dogs [blood urea nitrogen (BUN), 12-273] were studied. Azotemia was produced by bilateral uretero-venous anastomoses. The left renal vein and ureter were cannulated and renal blood flow (RBF) was measured by electromagnetic flowmeter. Simultaneous left renal clearances (C) of subpharmacological doses of TEA-14C and furosemide-14C were determined at seven 30-minute intervals. Initial loading doses were followed by continuous maintenance infusions. For TEA, clearance (1.5 ml/min-g +/- 0.2 S.E.M.) and extraction (E) (0.83 +/- 0.02) are independent of the degree of azotemia. Renal plasma flow (RPF), calculated as CTEA/ETEA, agreed closely with directly measured RPF (2.0 ml/g-min +/- 0.3). RPF was independent of azotemia. To allow for individual differences in the animals in RPF, the ratio CTEA/CF was used. CF (1.07-0.17 ml/min-g) and EF (0.54-0.06) decreased as a linear function of the increase in uremic serum: (see article). Furosemide and its principle metabolite were greater than or equal to 97% of the furosemide portion of the radioactivity. The metabolite did not increase with time in either plasma or urine. After acute administration of exogenous urea to two dogs (BUN 170 and 253) CTEA/CF was unrelated to BUN. Thus, the CF decreases proportionately with progressive azotemia and is not related to RBF, exogenous urea or metabolite. This suppression of renal tubular secretion of furosemide may partially account for reduced therapeutic efficacy of furosemide in azotemia.

The argon content of the martian atmosphere at the Viking 1 landing site is

Iron, calcium, aluminum, silicon, and sulfur are major elements in the first surface sample of Mars that has been analyzed by the Viking x-ray fluorescence spectrometer. Titanium is present in minor quantities. This is consistent with the sample being a mixture of fine silicate and oxide mineral grains, with a significant proportion of sulfates, possibly hydrated. Ferric oxide is regarded as the red pigmenting agent on the martian surface, but if it coats silicate grains, the coatings must be very thin (

Elemental analyses of fines in the Martian regolith at two widely separated landing sites, Chryse Planitia and Utopia Planitia, produced remarkably similar results. At both sites, the uppermost regolith contains abundant Si and Fe, with significant concentrations of Mg, Al, S, Ca, and Ti. The S concentration is one to two orders of magnitude higher, and K(<0.25 percent by weight) is at least 5 times lower than the average for the earth's crust. The trace elements Sr, Y, and possibly Zr, have been detected at concentrations near or below 100 parts per million. Pebblesized fragments sampled at Chryse contain more S than the bulk fines, and are thought to be pieces of a sulfate-cemented duricrust.

The relationship of natriuretic effect and furosemide excretion was studied in normal and azotemic dogs. Graded azotemia was produced in dogs by bilateral uretero-venous shunts of varying duration. The shunts were subsequently opened and urine and blood samples were taken to measure inulin, furosemide and sodium concentrations. Renal blood flow was measured by an electromagnetic flow probe. Two groups of dogs, control and experimental, were studied. The experimental group received a loading dose followed by a constant infusion of furosemide. This dose produced a natriuresis in nonazotemic normal dogs. The magnitude of this natriuresis correlated with furosemide excretion rate (P less than .005) and not with the plasma concentration of the drug. Furosemide clearance and extraction were inversely correlated with blood urea nitrogen. In the furosemide-treated group the augmentation of sodium excretion was not impaired except at blood urea nitrogen concentrations of greater than 200 mg/dl (two dogs). Thus the reduced clearance of furosemide may account in part for the high dose necessary. Further studies appear to be in order to clarify the relationship of the natriuretic response to furosemide to the rate of urinary excretion and plasma concentration of the drug.

An oral histidine loading test (100 mg L-His/kg body weight) was performed in 8 deaf patients with low histidase activity in the str. corneum of the skin. Beside an elevated plasma phenylalanine level resulting in a Phe/Tyr-quotient of 1,09 +/- 0,15 the basal level of histidine was slightly enhanced in patients with deafness, but without statistical significance. After histidine loading no differences of the histidine tolerance curves could be observed suggesting the heterozygosity state for histidinaemia. Thin-layer chromatographic investigation of imidazole compounds revealed some abnormal findings after loading. The results are discussed with regard to the clinical and biochemical heterogeneity of histidinaemia.

More significant events occurred in the lives of patients during the three months before presentation in general practice with pain in the neck or back than in a control group of symptomless patients.These findings were obtained by the completion by patients of a short questionnaire and their significance is discussed.

Solitary renal cysts associated with hypertension and documented hyperreninemia are relatively uncommon. A 13 year old boy with these findings is described (pressure 160/120 mm Hg). Contrast studies of the urinary tract and arteriography with selective renal vein sampling demonstrated a solitary cyst in the right kidney. The ratio of plasma renin activity in the right renal vein to left renal vein (RRV:LRV) was 2.35:1. After drainage of the cyst, there was a marked reduction in both systolic and diastolic pressures (126/84 mm Hg). Hypertension has not recurred during 14 months' follow-up.

Chemical results from four samples of martian fines delivered to Viking landers 1 and 2 are remarkably similar in that they all have high iron; moderate magnesium, calcium, and sulfur; low aluminum; and apparently very low alkalies and trace elements. This composition is best interpreted as representing the weathering products of mafic igneous rocks. A mineralogic model, derived from computer mixing studies and laboratory analog preparations, suggests that Mars fines could be an intimate mixture of about 80 percent iron-rich clay, about 10 percent magnesium sulfate (kieserite?), about 5 percent carbonate (calcite), and about 5 percent iron oxides (hematite, magnetite, maghemite, goethite?). The mafic nature of the present fines (distributed globally) and their probable source rocks seems to preclude large-scale planetary differentiation of a terrestrial nature.

The amount of plasma proteins associated to erythrocytes was determined or calculated by using three different techniques. Thus, there are 3.48 X 10(12) g of protein in a single erythrocyte or 94.12 g of protein respectively in the total of all erythrocytes in a healthy man with a body weight of 70 kg. The mass of plasma protein associated to erythrocytes will decrease in case of immunocomplex aggregates or otherwise denatured plasma proteins being fixed to the erythrocyte surface so that from a purely calculating point of view protein amounts on a scale of up to 46% of all plasma proteins may enter the free blood plasma under extreme conditions. In this, an immediately efficient possibility of compensation is seen by the authors in case of an acute consumption of blood proteins.