Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients.

BACKGROUND: Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro- and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. PATIENTS AND METHODS: 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6h, 12h, 24h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. RESULTS: Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). CONCLUSION: The current study presents an image of the serum Il-6, 8 and 10 releases in multiple trauma patients in the very early post-trauma period. We could thereby demonstrate that interleukin levels can clearly differentiate the presence of hemorrhagic shock and subsequent massive blood product substitution, the development of multiple organ failure and clinical outcome. No significant connection to age, gender and brain injury could be detected. Most importantly, changes in interleukin levels can be observed in the very early posttraumatic phase, at the earliest 90 minutes after trauma.

An examination of the potential role of spider digestive proteases as a causative factor in spider bite necrosis.

Tissue necrosis following spider bites is a widespread problem. In the continental United States, the brown recluse (Loxosceles reclusa), hobo spider (Tegenaria agrestis), garden spider (Argiope aurantia) and Chiracanthium species, among others, reportedly cause such lesions. The exact mechanism producing such lesions is controversial. There is evidence for both venom sphingomyelinase and spider digestive collagenases. We have examined the role of spider digestive proteases in spider bite necrosis. The digestive fluid of A. aurantia was assayed for its ability to cleave a variety of connective tissue proteins, including collagen. Having confirmed that the fluid has collagenases, the digestive fluid was injected into the skin of rabbits to observe whether it would cause necrotic lesions. It did not. The data do not support the suggestions that spider digestive collagenases have a primary role in spider bite necrosis.

The influence of lipid composition and divalent cations on annexin V binding to phospholipid mixtures.

Annexin V is a 36-kDa protein which, it has been suggested, is a factor in protecting the vascular endothelium from attack by antibodies to other phospholipid-binding proteins. Competition between annexin V and beta2-glycoprotein I (beta2GPI) for phospholipid surfaces is complicated by empirical observations regarding alterations in binding to anionic phospholipid, primarily phosphatidylserine. In order to elucidate the effect of phospholipid composition and divalent cations (Ca(+2) and Mg(+2)) on annexin V binding to phospholipid, we used biotinylated annexin V and peroxidase-conjugated avidin D to probe the binding of annexin V to phospholipid-coated wells of polystyrene microtiter plates. Binding of annexin V to anionic phospholipid is Ca(+2)-dependent and, in its absence, annexin V was found to bind most avidly to 100% phosphatidylcholine in a saturable manner, followed by decreasing percentages of phosphatidylcholine. Ca(+2) was found to inhibit phosphatidylcholine binding and promote the binding of phospholipid mixtures containing phosphatidylserine. Phosphatidylserine (100%) did not bind annexin V as strongly as mixtures of 50% and 75% phosphatidylserine. The effect with Ca(+2) suggests saturation of Ca(+2)-binding sites on annexin V, reached under our experimental conditions at approximately 1 mM. Under the same conditions, Mg(+2) slightly enhanced the binding of all of the phospholipid compositions studied. Ca(+2)-dependent binding of annexin V was competitively inhibited by Mg(+2); 5 mM Mg(+2) reduced binding significantly (p < 0.0001 by ANOVA, p < 0.05 for post hoc test of 5 mM vs 0 mM). These data suggest that the translocation of membrane phospholipid under the dynamics of ion transport in vascular endothelium may alter annexin V binding.

Systolic pressure predicts plasma vasopressin responses to hemorrhage and vena caval constriction in dogs.

We have proposed that the reflex increase in arginine vasopressin (AVP) secretion in response to hypovolemia is due to arterial baroreceptor unloading. If arterial pressure is the key to the mechanism, the slope relating plasma AVP to arterial pressure should be the same in response to hemorrhage, a model of true hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC), a model of central hypovolemia. We tested this hypothesis in conscious, chronically instrumented dogs (n = 8). The mean coefficient of determination (r(2)) values obtained from the individual regressions of log AVP onto systolic pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were 0.953 +/- 0.009 and 0.845 +/- 0.047, respectively. Paired comparisons indicated a significant difference between the means (P < 0.05), hence, SP was used in subsequent analyses. The mean slopes relating the log of plasma AVP to SP in response to hemorrhage and IVCC were -0.034 +/- 0.003 and -0.032 +/- 0.002, respectively, and the means were not significantly different (P = 0.7). The slopes were not altered when the experiments were repeated during acute blockade of cardiac receptors by intrapericardial procaine. Finally, sinoaortic denervation (n = 4) markedly reduced the slope in both the hemorrhage and IVCC treatments. We conclude that baroreceptors monitoring arterial pressure provide the principal reflex control of AVP secretion in response to hypovolemia.

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs.

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.

Is the Gauer-Henry reflex important for immersion diuresis in men?

BACKGROUND: This study examines the relationship between the threshold for plasma vasopressin concentration [PVP] responses and diuresis (Gauer-Henry reflex), and tests the hypothesis that water intake would not influence diuresis. METHODS: Eight men (19-25 yr) underwent four treatments: euhydration in air (Eu-air), euhydration in water immersion (Eu-H2O), and with prior 3.6% hypohydration in air (Hypo-air), and hypohydration in immersion (Hypo-H2O). Ad libitum drinking was allowed during the 3-h experimental and 1-h recovery periods. RESULTS: Drinking was greatest during the first 10 min: 3.5 ml x kg(-1) with Hypo-air (450 ml x 3 h(-1)) and only 1.7 ml x kg(-1) (p < 0.05) with Hypo-H2O (235 ml x 3 h(-1)). At 1 h, concomitant [PVP] decreased from a control level of 6.6+/-1.5 to 4.0+/-1 .0 pg x ml(-1) (delta = 2.6 pg x ml(-1), p < 0.05) with Hypo-air, and from 5.9+/-0.6 to 2.3+/-0.2 pg x ml(-1) (delta = 3.6 pg x ml(-1), p < 0.05) with Hypo-H2O. Urine flow was unchanged from control level (<1.0 ml x min(-1)) with Hypo-air, Hypo-H2O, and Eu-air, but increased to 4-5 ml x min(-1) with Eu-H2O. Neither water intake volume nor urine flow was related to the magnitude of [PVP] depression. Regression of Uosm/Posm ratio on [PVP] and urine flow indicated that [PVP] above 2 pg x ml(-1) did not affect urine flow. Thus, ad libitum water intake in previously hypohydrated subjects did not affect urine flow or the decrease in [PVP]. The threshold [PVP] to initiate significant diuresis was about 2 pg x ml(-1), and significant diuresis can occur with no change in [PVP] maintained at about 1 pg x ml(-1) during immersion in euhydrated subjects. CONCLUSIONS: Thus, it appears that the Gauer-Henry reflex is not the major mechanism for immersion-induced diuresis. Clearly, other diuretic factors are also involved.

Binding of complement component C1q to anti-beta2 glycoprotein I antibodies from patients with antiphospholipid syndrome.

OBJECTIVE: To determine if anti-beta2 GPI reactive with surface-bound beta2 GPI can bind C1q, i. e. to determine whether surface-bound beta2 GPI-anti-beta2 GPI immune complexes can initiate the classical pathway of complement activation. METHODS: Beta2 GPI was bound to chemically-activated microtiter plates which had previously been shown to promote anti-beta2 GPI reactivity with bound beta2 GPI. Wells with surface-bound beta2 GPI (capped with bovine serum albumin) were then reacted with complement-inactivated sera from antiphospholipid syndrome patients (APS) or with control sera. Following removal of unbound serum components, the wells were incubated with biotinylated C1q and probed with peroxidase-conjugated avidin D. Bound C1q was detected at 450 nm using tetramethyl benzidine/peroxidase as a substrate system and expressed as absorbance units (Abs). RESULTS: The identified 20 APS with elevated anti-beta2 GPI: 4 with IgG only, 4 with IgM only, 1 with IgA only, 1 with IgG and IgA, 6 with IgG and IgM and 4 with IgG, IgA and IgM. C1q binding from 20 healthy controls was 0.039 +/- 0.029 (SD). Of the APS, 17/20 (85%) had Abs >5 SD above controls. The 3 APS with C1q Abs within normal limits had, respectively, IgM only (1), IgA only (1), and both IgG and IgM (1). Statistical analyses (Kruskal-Wallis followed by Dunn's post test) suggest differences in IgG and IgG + IgM groups compared to con (Kruskal-Wallis: p = 0.0002; Dunn's: con vs. IgG, p < 0.05; con vs. IgG + IgM, p < 0.01). CONCLUSIONS: Anti-beta2 GPI from APS appear to have a variable degree of C1q affinity. Those patients with strong C1q binding responses are likely to have an inflammatory component to their disease processes.

Modification of beta 2glycoprotein I by glutardialdehyde. Conformational changes and aggregation accompany exposure of the cryptic autoepitope.

Autoantibodies from patients with antiphospholipid syndrome (APS) recognize an epitope on beta 2glycoprotein I (beta 2 GPI) only when native beta 2 GPI is adsorbed on surfaces composed of anionic phospholipids or oxidized polystyrene. beta 2 GPI was modified with the crosslinking agent, glutardialdehyde (GDA), which induced exposure of the anti-beta 2 GPI epitope at GDA:beta 2 GPI mol ratios in the range of 500-2000. A second crosslinking agent, dimethyl-suberimidate (DMS), did not expose the epitope, which may be a consequence of its having less tendency than GDA to form intermolecular links. SDS-PAGE experiments demonstrate that GDA does promote extensive intermolecular crosslinking of beta 2 GPI, and DMS does not. Formaldehyde also reacts with the lysine residues of beta 2 GPI, but does not expose the epitope. The circular dichroism spectra of native and modified beta 2 GPI confirm that GDA induces changes in conformation that are qualitatively different from those caused by formaldehyde. These data provide evidence that binding of lysine residues is not a sufficient condition for exposure of the autoepitope, and also support the likelihood that anti-beta 2 GPI antibodies bind only to aggregates of the protein. Thus, by synthesizing an active holoantigen of beta 2 GPI, conditions were defined that are necessary for binding of human autoantibodies.

Arterial baroreceptors control blood pressure and vasopressin responses to hemorrhage in conscious dogs.

The goal of this study was to determine the role of arterial baroreceptors in the reflex control of arginine vasopressin (AVP), renin, and cortisol secretion in response to a 30-ml/kg hemorrhage in conscious dogs. The hormonal responses were measured in six dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD + CD. In the intact condition, mean arterial pressure (MAP) was maintained at control levels until blood loss reached 20 ml/kg and the absolute magnitude of the fall at 30 ml/kg was 35 +/- 10 mmHg. Similar responses were obtained during acute CD. In contrast, MAP fell earlier (at 5 ml/kg, P < 0.05) and to much lower levels in both the SAD and SAD + CD conditions. The individual slopes relating systolic pressure to plasma AVP, renin activity (PRA), and cortisol were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating AVP to systolic pressure but no effect of CD and no SAD x CD interaction. In contrast, there was no effect of either SAD or CD on the relationship between PRA or plasma cortisol and systolic pressure. These results indicate that maintenance of blood pressure and the normal pattern of AVP secretion during hemorrhage depend on intact arterial baroreceptor reflexes.

Standardized measurement of major immunoglobulin class (IgG, IgA, and IgM) antibodies to beta2glycoprotein I in patients with antiphospholipid syndrome.

Patients with the antiphospholipid syndrome (APS) have autoantibodies directed against epitopes on beta2 glycoprotein I (beta2GPI). We describe herein the performance characteristics of standardized enzyme-linked immunosorbent assays (ELISAs) for anti-beta2GPI of the three major immunoglobulin classes: IgG, IgA, and IgM. All three assays generated highly linear standard curves (5 points, r > or = 0.993 for each); precision was excellent both intra-assay and run-to-run, with coefficients of variation (CV) ranging from 2.3% to 6.6%. Values for IgG anti-beta2GPI correlated strongly with those obtained by an earlier method (r = 0.80, P< 0.0001). A study group consisting of 203 healthy subjects was used to generate percentile-based reference intervals for all three classes of anti-beta2GPI. APS subjects' anti-beta2GPI were found to differ significantly (P <0.0001 for each) from those of the control population. All three assays correlated well with beta2GPI-dependent anticardiolipin antibody (aCL) measurements; IgG: r = 0.94 (P <0.0001), for IgA: r = 0.82 (P<0.001) and for IgM: r = 0.84 (P<0.0001). We suggest that these ELISAs may provide valuable standardized measurements of IgG, IgA, and IgM anti-P2GPI.

Hemodynamic and hormonal responses to hemorrhage in conscious rabbits at mid- and late gestation.

This study tests the hypothesis that conscious rabbits late in pregnancy (P), but not at midgestation (MP), are less able to maintain arterial pressure during hemorrhage. Blood volume (BV) was elevated (P < 0.05) by an average of 13 +/- 4 (MP) and 35 +/- 3% (P). Rabbits were bled in both the nonpregnant (NP) and P state at 2% of the initial BV per minute. The hemorrhage was stopped after arterial pressure decreased. In NP rabbits, arterial pressure was well maintained near control pressures of 70 +/- 2 mmHg until 38 +/- 2% of the initial BV was removed and then rapidly fell to reach a nadir at 35 +/- 2 mmHg. In contrast, in P rabbits, basal arterial pressure was lower (61 +/- 2 mmHg; P < 0.05) and gradually decreased to below control after <25% of the initial BV was removed. Moreover, the rapid hypotensive phase was triggered with a lower percent BV removal (33 +/- 2%; P < 0.05). Basal heart rate was higher during P (149 +/- 5 vs. 189 +/- 9 beats/min; P < 0.05), and reflex increases were delayed. The slope of the relationship between arterial pressure and vasopressin was not modified during P, although the line was shifted to a lower pressure (P < 0.05). Larger increases in plasma renin activity and ANG II concentration were produced during hemorrhage in P rabbits. In contrast, no differences in the changes in arterial pressure, heart rate, and vasopressin were found between NP and MP rabbits during hemorrhage, although increases in renin and ANG II were greater at MP (P < 0.05). In summary, although P conscious rabbits are less able to maintain blood pressure during hemorrhage, this change is not evident at MP. These data suggest that the factors that mediate the P-induced alterations in arterial pressure regulation are not operative until late in gestation.

Plasma volume expansion with oral fluids in hypohydrated men at rest and during exercise.

BACKGROUND: The purpose for this study was to evaluate various carbohydrate (CHO)-electrolyte fluid formulations for consumption by astronauts to maintain or restore their plasma volume (PV) and total body water (TBW) during and after extravehicular activity (exercise experiment, EE) and for a few hours before reentry and immediately after landing (rest experiment RE). HYPOTHESIS: That fluid formulation electrolyte content would be more important than osmotic (Osm) content for increasing or maintaining PV during the RE and EE. METHODS: In the RE, 5 healthy men (23-44 yr), previously dehydrated for 24 h, drank 6 fluid formulations (Water, 19.6 Na, 157 Na, 19.6 Na + glucose, and the prepared drinks Performances and Power)--one each at weekly intervals, and then sat for 70 min. In the EE, four healthy 24-h dehydrated men (30-46 yr) exercised for 70 min supine on a cycle ergometer (load = 71 +/- 1% peak VO2). RESULTS: Rest: Subjects who consumed formulations with total Osm concentrations nearer the normal range (157 Na - 270 mOsm x kg(-1), Performance with 19.6 mEq x L(-1) Na - 380 mOsm, and to some extent Power with 23.5 mEq x L(-1) Na - 390 mOsm) had the greater increases in PV; intake of drink 157 Na, with the largest Na content, induced the greatest hypervolemia of 7.6% (p < 0.05). The various additional ions, in addition to 19.6 Na, probably contributed to the 4.6% (p < 0.05) hypervolemia with Performance. Water was not effective. Exercise: Stabilization of PV between 15-70 min was not related to drink total CHO, Na or Osm content. Performance and 157 Na were no more effective than 19.6 Na or 19.6 Na + glu for PV stabilization. Water was the least effective. Regulatory mechanisms controlling PV during exercise appear to be independent of oral fluid formulation Osm-electrolyte content. CONCLUSIONS: Drink cation (sodium) content is more important that its total osmotic content for increasing plasma volume at rest. Fluid formulations with greater hypervolemic action in resting subjects may not be as effective during exercise; therefore different formulations for use during exercise appear to be necessary.

A stable, multi-subunit complex of beta2glycoprotein I.

Beta2glycoprotein I (beta2GPI) is a 54-kDa plasma protein which is recognized as an autoantigen for antibodies from patients with antiphospholipid syndrome (APS). SDS-PAGE (under reducing conditions) of beta2GPI from three sources indicates that the 54-kDa beta2GPI band is accompanied by a band corresponding to an 8-kDa protein. In the absence of detergent and reducing agents (native PAGE), beta2GPI demonstrated a large complex (molecular mass approximately 320 kDa) which is dissociable by boiling in 6-8 M urea, yielding several lower molecular mass bands, one of which corresponds to the 8-kDa protein observed in SDS-PAGE. Sera from five healthy adults demonstrated native beta2GPI migration equivalent to the commercially purified protein. Atomic force microscopy (AFM) images of native beta2GPI show aggregrates of particles each having a diameter of 30-35 nm. This is consistent with a globular unit the size of which would be substantially larger than that expected for a 54-kDa protein. These experiments suggest that the 54-kDa beta2GPI monomer subunits exist as a multimeric complex with the 8-kDa protein.

Phospholipid-independent binding of beta 2glycoprotein I by IgA from patients with antiphospholipid syndrome.

beta 2glycoprotein I (beta 2GPI) is a phospholipid-binding protein of the coagulation system. In patients with the antiphospholipid syndrome (APS), antibodies to beta 2GPI contribute to the population of "antiphospholipid antibodies" measured in the anticardiolipin antibody (aCL) assay. In fact, both IgG and IgM antibodies from patients with APS bind beta 2GPI in the absence of anionic phospholipids if the antigen is bound to a suitable surface, i.e., one which exposes the epitope. The binding of IgA was studied from patients with APS, using an enzyme-linked immunosorbent assay (ELISA), and significantly higher binding of IgA was observed from 39 patients compared to a control group of 50 healthy individuals (p < 0.0001). Moreover, 15 out of 39 APS subjects (38 percent) exhibited binding greater than 5 standard deviations (SD) above the mean of the control group. All 39 APS patients had elevated IgG anti-beta 2GPI; however, depletion of IgG from two APS sera diminished, rather than enhanced, binding of IgA. Pre-incubation with purified IgG from a subject with APS led to inhibition of IgA binding at inhibitor levels > 125 micrograms IgG/well. These data demonstrate that patients with APS have IgA anti-beta 2GPI autoantibodies and that the epitope(s) which are recognized by these antibodies can be presented in the absence of cardiolipin or other anionic phospholipids.

Reduction of pituitary AVP and OT contents in rats following spaceflight.

BACKGROUND: Responses of pituitary concentrations of vasopressin (AVP) and oxytocin (OT) during spaceflight have been variable, possibly due to differences in flight conditions or in age and strain of flight animals. METHODS: We reviewed findings of three space-flights of varying flight and recovery durations in which rats of different ages and strains were used. Male rats ranging in weight from 248-396 g were flown in space for 7-14 d. Flight animals were then compared with vivarium controls and synchronous controls. Parallel ground-based studies (hypergravity and simulated hypogravity) were conducted. RESULTS: Pituitary content of AVP was significantly (p < or = 0.05) decreased by spaceflight (6.3 +/- 0.3 micrograms.mg-1 protein in flight vs. 8.3 +/- 0.5 micrograms.mg-1 protein in vivarium). OT content was also reduced during spaceflight (4.3 +/- 0.2 micrograms.mg-1 protein in flight vs. 6.1 +/- 0.3 micrograms.mg-1 protein in vivarium). Vivarium and synchronous control rats showed no difference in pituitary contents. Flight duration or recovery times did not appear to influence pituitary hormone contents. Strain of rat had an effect on content but not on responses to spaceflight. Age of animals confounded the response to spaceflight: pituitary contents of AVP and OT were not altered in young animals (< or = 60 d old). Hindlimb suspended animals showed no difference in AVP but OT content was decreased. Ground-based exposure to hypergravity (2 G) did not alter content of AVP or OT in young animals. CONCLUSIONS: Decreases in pituitary content of AVP and OT with spaceflight may be due to a variety of factors unique to the microgravity environment. Differences between studies may be due in part to differences in size and age of rats used.

The association of antibodies to beta 2 glycoprotein I with the antiphospholipid syndrome: a meta-analysis.

The precise target of marker autoantibodies in the antiphospholipid syndrome (APS) has been controversial. Recently, the theory that surface-bound beta 2 glycoprotein I (beta 2 GPI) presents a normally encrypted autoepitope and that antibodies to beta 2 GPI (anti-beta 2 GPI) are associated with APS, has been prominent. The literature has been searched from 1990 to 1995 (inclusive) to find studies in which: (1) anti-beta 2 GPI antibodies were measured and, (2) adequate clinical data describing the patients were included. These conditions were met in four studies, from August 1992 to December 1995, in which patient samples ranged from 15 to 39 cases, the total of the four studies being 90 cases. Applying the diagnostic criteria of > or = 2 clinical manifestations of APS, 65 cases had APS while 25 did not. For the group with APS, 58/65 (89 percent) were anti-beta 2 GPI (+); among those who did not meet the criteria, 11/25 (44 percent) were anti-beta 2 GPI (+) (p < 0.0001). The presence of either the primary (1 degree) or secondary (2 degrees) form of APS made no difference in association with anti-beta 2 GPI; 13/16 (81 percent) patients with 1 degree APS and 45/49 (92 percent) with 2 degrees APS had anti-beta 2 GPI. The presence of lupus anticoagulant (LAC) did not predict APS: 25/58 (38 percent) APS (+) cases were LAC (+); 11 APS (-) were all LC (+) (p < 0.0001). IgG anticardiolipin also showed a closer association with APS absence (25/25 cases; 100 percent) than with APS presence (40/65; 62 percent, p < 0.0001). These data support the contention that anti-beta 2 GPI antibodies are closely associated with APS and that their measurement may facilitate the diagnosis.

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats.

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

Antibodies to beta 2 glycoprotein I: standardized immunoassay and a reference interval for healthy controls.

Patients with antiphospholipid syndrome (APS) demonstrate an antibody reactivity with beta 2 glycoprotein I (beta 2 GPI) independent of the anionic phospholipids that previously had been believed to be the relevant autoantigens associated with this syndrome. Immunoassays for IgG anti-beta 2 GPI have, however, suffered from a lack of standardization. In this article, we describe an assay based on reference standards that we developed recently. The assay exhibits excellent linearity, with regard to both application of the standards and dilution of out-of-range specimens. Precision was assessed both within the between run and was judged to be satisfactory. A reference interval was developed on the basis of a control group consisting of 111 men and 93 women, yielding a range of 0-19 standard IgG anti-beta 2 GPI units (SGU) for the ninety-fifth percentile of values. These data suggest that this standardized anti-beta 2 GPI assay may be useful in the clinical diagnostic laboratory.

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

BACKGROUND/HYPOTHESIS: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used. METHODS: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz). RESULTS: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4. CONCLUSIONS: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.