Gas gangrene occurring soon after compound depressed skull fracture

Summary A retrospective evaluation of the prognostic value of different parameters available in patients affected by glial tumours and submitted to serial stereotactic biopsy is presented. The series investigated includes thirty-three untreated patients with proven brain gliomas submitted to stereotactic biopsy. All patients have been clinically and neuroradiologically monitored for three years. The factors investigated belong either to the preoperative data (clinical history and symptomatology, CT pattern and volume of the lesion) or to histological and biological data obtained after the stereotactic biopsy. The results suggest the need of a multimodal prognostic evaluation in glial tumours and particularly stressed is the accuracy of prognostic indications derived from cell kinetic studies.Presented at the European Congress of Neurosurgery, Barcelona, September 1987.     

输送链的结构与齿形探讨(三)——修正齿形链传动特性及完善齿形修正设计

本文讨论用“包络一轨迹”法设计的修正齿形链的传动特性,并提出了完善齿形修正设计的方法,基本上实现消除链传动申的“多边形效应”。     

Factors affecting serotonin uptake into human platelets

Because of complexities in platelet serotonin uptake dynamics, we studied the influence of the time of day and year as well as the subject's age on uptake parameters. While the assay itself was quite reproducible, and the kinetic parameters of 5 HT uptake were stable over a few days, at a given time, within an individual, the variance was quite large when samples from different times of the day or year or from different individuals were compared. An inverse relationship between V _max (moles/cell number/time) and platelet number was found in data from a group of individuals, suggesting regulation of V _max not at the level of uptake capacity per cell, but in a manner that somehow takes into consideration the number of platelets in the subject's plasma. Indeed, expressing V _max in a new way (called total V _max), not based on V _max per cell or per 10⁷ cells but for the total number of platelets in the volume of PRP used, greatly reduced the scatter in the between-individuals and across-time data. While V _max (moles/cell number/time) exhibited only a trend toward reduction with age, for example, the decline in total V _max with subject age was statistically significant. It is suggested that total V _max (moles/time) may be a more physiologically relevant expression for an uptake function than V _max (moles/time/cell number).     

Effects of lysophosphatidylcholine and arachidonic acid on the regulation of intracellular Ca2+ transport

Summary The role of lysophosphatidylcholine and arachidonic acid in signal transduction was investigated using subcellular organelles and permeabilized cells from liver. Both substances can be generated intracellularly by the action of phospholipase A₂ on phosphatidy1choline. Lysophosphatidylcholine as well as arachidonic acid raised the free Ca²⁺ concentration in the incubation media of permeabilized cells, isolated mitochondria and microsomes. The half maximally effective concentrations for Ca²⁺ release from mitochondria were 78 ± 1 mol/l for lysophosphatidylcholine and 80 ± 11 mol/l for arachidonic acid. Though isolated microsomes released Ca²⁺ in response to both agents, the combined presence of mitochondria and microsomes did not exhibit a synergism in Ca²⁺ release in response to arachidonic acid; the increase in the free Ca²⁺ concentration in response to lysophosphatidylcholine was even smaller than with mitochondria alone. It is concluded that the two reaction products of phospholipase A₂ can raise the cytoplasmic Ca²⁺ concentration and therefore may participate in cellular signal transduction. Send offprint requests to I. Rustenbeck at the above address     

Evaluation of theophylline pharmacokinetics in a pediatric population using mixed effects models

Routine clinical pharmacokinetic data collected prospectively from pediatric patients receiving theophylline were analyzed using the NONMEM (nonlinear mixed effects model) digital computer program. A total of 314 measured serum theophylline concentrations (STCs) were obtained from 84 hospitalized patients ranging in age from 4 months to 15.2 years with the majority of patients between the ages of 1 and 8 years. Fifty-six percent were male. The race/ethnicity distribution was 71.4% Latin, 15.5% black, 11.9% Caucasian, and 1.2% (one subject) Pakistani. Of the total number of observed STCs, 16.2% reflected some degree of outpatient dosing. The pharmacokinetic model used was a one-compartment open model with either zero-order or first-order absorption and first-order elimination. Age was the most important determinant of theophylline clearance (Cl);weight was inferior to age and did not statistically improve the model (p>0.005when combined with age. Total Clincreased by 10%/year over the age range of 1 to 15 years of age. Black race and male gender were associated with higher Clvalues: for a given age, Clwas 34% higher for blacks than the reference population composed of the remaining patients, and Clfor males was 25% higher than that for females. The volume of distribution (Vdfor the population was estimated to be 0.62 L/kg. The interindividual variability in Cland Vdexpressed as coefficients of variation were 19 and 28%, respectively. The residual intraindividual error variance corresponded to a standard deviation of 2.8 g/ml. The STCs that represented some degree of outpatient dosing were 21 % lower than those reflecting only inpatient dosing. Alternate models that include weight as a determinant of theophylline clearance are also provided. The NONMEM method of determining population pharmacokinetics is well suited to the pediatric population since it does not require a large number of STCs per patient. In this study a mean of only 3.7 STCs per patient were utilized to provide information which should prove useful in the design and adjustment of theophylline dosage regimens in children.     

The effect of harmaline on intestinal sodium transport and on sodium-dependentd-glucose transport in brush-border membrane vesicles from rabbit jejunum

Harmaline inhibition of sodium uptake and of sodium-dependentd-glucose transport was investigated using brush-border membrane vesicles from frozen rabbit jejunum. Under sodium-gradient conditions, initiald-glucose uptake (20 s) was inhibited by harmaline at concentrations above 0.5 mM, but at lower harmaline concentrationsd-glucose uptake was stimulated by 10–15%. When a similar potassium gradient was used, harmaline had no effect. At concentrations upt to 2 mM, harmaline did not alter the equilibrium uptake ofd-glucose ord-mannitol. After pre-equlibration with sodium (25 mM),d-glucose uptake was inhibited at harmaline concentrations ranging from 0.1 to 2 mM. Sodium (10 mM) uptake was also inhibited by harmaline. Increasing the sodium concentration reduced the inhibitory effect of harmaline on tracer sodium uptake as well as on sodium-dependentd-glucose uptake. Similar to phlorizin, harmaline (1 mM) was able to prevent glucose-induced sodium influx across the brush-border membrane.Sodium uptake into brush-border membrane vesicles seems to be inhibited at lower harmaline concentrations than sodium-dependentd-glucose uptake. At high (2 mM) inhibitor concentrations, however, sodium-dependent glucose uptake is more strongly inhibited than sodium uptake. These results suggest that harmaline inhibits both sodium and sodium-dependent transport across intestinal brush-border membranes by interacting with specific sodium-binding sites.     

Advection and Diffusion of Substances in Biological Tissues With Complex Vascular Networks

For highly diffusive solutes the kinetics of blood–tissue exchange is only poorly represented by a model consisting of sets of independent parallel capillary–tissue units. We constructed a more realistic multicapillary network model conforming statistically to morphometric data. Flows through the tortuous paths in the network were calculated based on constant resistance per unit length throughout the network and the resulting advective intracapillary velocity field was used as a framework for describing the extravascular diffusion of a substance for which there is no barrier or permeability limitation. Simulated impulse responses from the system, analogous to tracer water outflow dilution curves, showed flow-limited behavior over a range of flows from about 2 to 5 ml min^–1 g^–1, as is observed for water in the heart in vivo. The present model serves as a reference standard against which to evaluate computationally simpler, less physically realistic models. The simulated outflow curves from the network model, like experimental water curves, were matched to outflow curves from the commonly used axially distributed models only by setting the capillary wall permeability–surface area (PS) to a value so artifactually low that it is incompatible with the experimental observations that transport is flow limited. However, simple axially distributed models with appropriately high PSs will fit water outflow dilution curves if axial diffusion coefficients are set at high enough values to account for enhanced dispersion due to the complex geometry of the capillary network. Without incorporating this enhanced dispersion, when applied to experimental curves over a range of flows, the simpler models give a false inference that there is recruitment of capillary surface area with increasing flow. Thus distributed models must account for diffusional as well as permeation processes to provide physiologically appropriate parameter estimates. © 2000 Biomedical Engineering Society. PAC00: 8719-j, 8710+e     

Sodium gradient-energized concentrative transport of adenosine in renal brush border vesicles

The uptake of adenosine in brush border vesicles of the proximal tubule of the rat kidney has been studied with a filtration technique. The initial rate of uptake was almost 6 times greater in the presence of NaCl than in the presence of KCl. The stimulatory effect of Na⁺ was strictly dependent on a gradient of Na⁺ (out>in). The time course of uptake showed an overshoot with a maximum at 20 s with a gradient of NaCl, but not with KCl. Inosine and 5-AMP were produced from adenosine within the vesicles. In the presence of an inhibitor or adenosine deaminase adenosine was not significantly metabolized during the first 20 s of uptake. Thus, kinetic parameters of transport could be studied in the absence of interferences with metabolism. AK _m of 1.1 M and aV _max of 232 pmol · min^–1 · mg protein^–1 were calculated for the Na⁺ gradient-dependent transport. The dependency on a Na⁺ gradient, the capacity for uphill transport and the high affinity for adenosine situate this transport system apart from the mechanisms of transport of nucleosides described so far. It may be relevant in regard to the role of adenosine in the regulation of glomerular filtration.Abbreviations used EHNA erythro-9-(2-hydroxy-3-nonyl)adenine - FCCP carbonylcyanide p-trifluoromethoxy-phenylhydrazone - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - Tris tris (hydroxymethyl)-aminomethane     

Macrophage and perisinusoidal cell kinetics in acute liver injury.

Perisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride-induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear-incorporated bromodeoxyuridine. The results showed an expansion of the desmin-positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages.     

HnRNP CBP35-CBP67 interaction during stress response and ageing

Previous studies have demonstrated the existence of nuclear carbohydrate binding proteins in a variety of mammalian cells with molecular masses of 35 000, 67 000, and 70 000 (CBP35, CBP67, and CBP70), which are associated with nuclear ribonucleoprotein (RNP) complexes. CBP35 consists of two domains, an aminoterminal portion that is homologous to certain regions of proteins of the heterogeneous nuclear RNP complex, and a carboxyl-terminal portion homologous to β-galactoside-specific lectins. CBP35 it has been proposed, like the glucose-specific lectin, CBP67, to guide RNP complexes through the nuclear pore. Here we show that the exposure of mature rats to stress induces an increase in nuclear CBP35 bound to CBP67 and retained on immobilized glucose. Nuclear extracts from the livers of old rats displayed no detectable stress response. This CBP35·CBP67 association detected in rat liver is considered with respect to the CBP35·CBP70 association recently observed in HL60 cell nuclear extracts.