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[Antiphospholipid syndrome with only antiphosphatidylethanolamine antibodies: report of 20 cases].

PURPOSE: The association of antiphosphatidylethanolamine antibodies (aPE) as the only antiphospholipid antibody with antiphospholipid syndrome (APS) is discussed. The aPE was described as the sole antibody in many cases suggesting APS. aPE was not included in the Sapporo criteria for the classification of APS. METHODS: We investigated the clinical features of 20 patients with aPE only; 17 patients had symptoms potentially related to APS (group 1) and three had other manifestations (group 2). RESULTS: There were 15 women and five men, mean age was 35 +/- 12 years at the beginning. In group 1 (n = 17), ten patients presented arterial thrombosis, nine venous thrombosis (five had both), and six microvascular thrombosis (livedo reticularis, lacunar pathology). The aPE positivity was persistent in 13 patients. A subgroup of four patients (three women) presented arteriosclerosis with peripheral arteriopathy which started before 45 years of age. They had another atherosclerosis risk factor associated with aPE persistence. In group 2 (n = 3), there was no thrombotic event, one demyelinating pathology, one microvascular pathology, and one arterial dysplasia. The aPE positivity was never confirmed. Finally, 13 patients presented an APS with aPE only, confirmed at least 8 weeks later. CONCLUSIONS: Our study points out that testing for aPE would be of interest for patients when symptoms were potentially related to APS, particularly when other antiphospholipid antibodies were negative. This description questions the enlargement of the APS biological criteria defined in Sapporo. The role of aPE in atherosclerosis is considered.

Adult↗

Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies.

Antiphosphatidylethanolamine antibodies (APE) have been described in patients with thrombotic diseases and recurrent pregnancy loss (RPL). It has been reported that certain APE are not specific for phosphatidylethanolamine (PE) per se, but are directed to PE-binding plasma proteins, called kininogens. Our recent in vitro data suggest that APE may recognize the domain 3 (D3) region of kininogens. In this study, we have used synthetic peptides that span the D3 of kininogens in inhibition and direct binding studies to identify epitopes that are sites for binding APE. Our present data demonstrate that among 24 RPL patients who were positive for kininogen-dependent immunoglobulin (IgG) APE, 17 patients (70.8%) recognized the LDC27 peptide. We mapped the APE-binding region on D3 using plasma from a RPL patient (X) who had a high titer of IgG APE that recognized LDC27. APE of patient X recognized a 13-residue segment in LDC27, named CNA13. Leu331-Met357 (LDC27) and Cys333-Lys345 (CNA13) are located on the carboxyl-terminal portion of kininogen D3, which is known as the major kininogen heavy chain cell attachment site where it overlaps its cysteine protease inhibitory region. Because APE interferes with the balance of hemostasis in vitro, APE may therefore induce a similar condition in patients thereby causing thrombosis and RPL.

Abortion, Habitual↗

Inhibition by apple polyphenols of ADP-ribosyltransferase activity of cholera toxin and toxin-induced fluid accumulation in mice.

The effects of crude polyphenol extracted from immature apples on the enzymatic and biological activities of a cholera toxin (CT) were investigated. When the apple polyphenol extract (APE) was examined for properties to inhibit CT-catalyzed ADP-ribosylation of agmatine, it was found that APE inhibited it in a dose-dependent manner. The concentration of APE to inhibit 50% of the enzymatic activity of CT (15 microg/ml) was approximately 8.7 microg/ml. The APE also diminished CT-induced fluid accumulation in two diarrhea models for in vivo mice. In the ligated ileum loops, 25 microg of APE significantly inhibited fluid accumulation induced by 500 ng of CT. In a sealed mouse model, even when APE was administered orally 10 min after a toxin injection, fluid accumulation was significantly inhibited at a comparable dosage. Lineweaver-Burk analysis demonstrated that APE had negative allosteric effects on CT-catalyzed NAD: agmatine ADP-ribosyltransferase. We fractionated the APE into four fractions using LH-20 Sephadex resin. One of the fractions, FAP (fraction from apple polyphenol) 1, which contains non-catechin polyphenols, did not significantly inhibit the CT-catalyzed ADP-ribosylation of agmatine. FAP2, which contains compounds with monomeric, dimeric, and trimeric catechins, inhibited the ADP-ribosylation only partially, but significantly. FAP3 and FAP4, which consist of highly polymerized catechin compounds, strongly inhibited the ADP-ribosylation, indicating that the polymerized structure of catechin is responsible for the inhibitory effect that resides in APE. The results suggest that polymerized catechin compounds in APE inhibit the biological and enzymatic activities of CT and can be used in a precautionary and therapeutic manner in the treatment of cholera patients.

ADP Ribose Transferases↗

Apurinic/apyrimidinic endonuclease-1 protein level is associated with the cytotoxicity of L-configuration deoxycytidine analogs (troxacitabine and beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine) but not D-configuration deoxycytidine analogs (gemcitabine and beta-D-arabinofuranosylcytosine).

Beta-L-dioxolane-cytidine (L-OddC, BCH-4556, Troxacitabine), a novel L-configuration deoxycytidine analog, is under phase III clinical trial for cancer treatment. We showed that human apurinic/apyrimidinic endonuclease (APE-1) has exonuclease activity for preferentially removing L-OddC and other L-configuration nucleosides over D-configuration nucleosides from the 3' terminus of DNA in vitro. In this study, we examined whether APE-1 protein plays a role in the cytotoxicity of L-OddC. We established RKO (human colorectal carcinoma) cell lines that can be induced by doxycycline to overexpress 4- to 5-fold either APE-1 wild type (wt), C65A (redox deficient), E96A (exonuclease deficient), or E96Q (exonuclease deficient) mutants and to down-regulate endogenous APE-1 by short hairpin RNA to 10% of the original level. Clonogenic results indicated that the induction of wt or C65A, but not E96A or E96Q, made cells approximately 2-fold resistant to L-OddC and beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (L-Fd4C), whereas the down-regulation of APE-1 sensitized cells by approximately 2-fold to L-OddC and L-Fd4C. The alteration of APE-1 in cells did not change the sensitivity of these cells to beta-D-2',2'-difluorodeoxycytidine (dFdC; gemcitabine) and beta-D-arabinofuranosylcytosine (AraC), both of which are D-configuration deoxycytidine analogs. The DNA incorporation of L-OddC, but not that of dFdC, was decreased by the induction of wt APE-1 but not E96A mutant and was increased by the down-regulation of APE-1. The rate of retention of L-OddC was inversely correlated to the level of APE-1 in isolated nuclei; however, this was not the case for dFdC. In conclusion, this study supports the hypothesis that APE-1 plays a critical role in the actions of L-configuration but not D-configuration nucleoside analogs.

Cell Line, Tumor↗

[Anti-phosphatidylethanolamine antibodies in patients with Sneddon's syndrome].

Anti-phosphatidylethanolamine antibodies (aPE) belong to the group of anti-phospholipid antibodies (aPL) and are directed against neutral phospholipid, connected with co-factor protein, while cardiolipin antibodies (aKL) are directed against negative phospholipid. The paper presents a study of prevalence and clinical significance of IgG aPE in 28 patients (22 women and 6 men, mean age 47.6 +/- 11.6 years) with Sneddon's syndrome (SS), which consists in cerebrovascular disturbances and extensive livedo reticularis. IgG aPE were detected by immune-enzyme assay. The upper normal limit, calculated as mean + 3SD after studying 19 healthy donors, was 0.303 optic density units. aPE were found in 15 (54%), aKL and/or lupus anticoagulant (LA)--in 6 (21%) patients with SS. aPE were found in 10 (46%) out of 22 aKL- and LA-negative patients. Among the aPE-positive patients there was a higher incidence of cortic dementia (53% vs. 8%, p = 0.02), the widening of cortical sulci, detected by means of computed tomography and magnetic resonance imaging (73% vs. 31%, p = 0.05), and mild renal syndrome (73% vs. 16%, p = 0.03). Besides, they displayed a higher rate of headaches (87% vs. 62%), chorea (33% vs. 8%), epilepsy (27% vs. 8%), non-carrying of pregnancy (91% vs. 50%), peripheral venous thrombosis (27% vs. 15%), coronary heart disease (47% vs. 31%), cardiac valvular thickening, detected by means of EchoCG (93% vs. 69%), arterial hypertension (87% vs. 54%), thrombocytopenia (20% vs. 0), anemia (40% vs. 15%); however, the difference was not significant. The results show that aPE detection, performed in addition to detection of classic immunological antiphospholipid syndrome markers (aKL and LA), increases the portion of aPE-positive patients with SS by 33%. aPE are often (in 46% of cases) found in aKL- and LA-negative patients with SS. aPE is likely to be the most significant factor of thrombosis in small arteries of the brain cortex and kidneys, which could explain their association with dementia and renal syndrome.

Adult↗

Morphometric analysis of the distal humerus of some Cenozoic Catarrhines: the Late Divergence Hypothesis revisited.

Washburn's Late Divergence Hypothesis (LDH) makes a series of predictions about the phyletic affinities of extant hominoids and also predicts the locomotor behavior of the "formative ape," the common ancestor to the African apes and humans, and of the earliest hominids. The present study explores some of these predictions in the light of distal humerus morphology. Multivariate analysis of distal humerus metrics, corrected for the within-groups distortion of shape by size, was used to compare a broad sample of 22 modern anthropoid taxa with 15 fossils from the Fayum, Rusinga Island, Ft. Ternan, Neudorf an der March, Kanapoi, Kromdraai, Lake Turkana, and Hadar. The results of this analysis support some aspects of the LDH, while other aspects are unresolved. Specifically, the distal humeri of the large hominoids are very distinct from those of other anthropoids; however, Hylobates is not associated clearly with either hominoids or monkeys. This suggests that "brachiation" (sensu Hylobates) is too specialized a behavior and cannot explain the common set of characteristics known to unify the hominoids. Among the large apes, there is no discrimination that can be made between the African apes and Pongo, and Homo appears only slightly closer to Pongo than to the other apes. This offers little insight into the question of whether humans did, or did not, go through a "knuckle-walking" stage in their ancestry. The Oligocene and Miocene distal humeri sustain Washburn's assertion that the "formative apes" resembled the suspensory quadrupedal platyrrhines like Ateles. The Miocene P. africanus specimen highlights the uniqueness of Hylobates in showing that this fossil "bridges" the morphology of the acrobatic cebids and the morphology of the larger apes; it appears to be clearly "intermediate" between the two groups. Hylobates, by contrast, has affinities with no fossil, does not connect with the apes, and is generally isolated except for its connection with colobines. Among the Plio-Pleistocene fossils, the Hadar sample proves to be quite primitive, and may be close to the point where hominids and pongids diverged. The Kanapoi distal humerus (KP 271), far from being more "human-like" than Australopithecus, clearly associates with the hyperrobust Australopithecines from Lake Turkana. The stratigraphically late Kromdraai distal humerus is the only hominid to be projected near Homo. The Plio-Pleistocene hominids generally evince a pattern consistent with the prediction of a late separation of hominids and pongids. But, the results of this study, like many before it, fail to resolve the central question of whether the last common ancestor of the African apes and humans "knuckle-walked." It is suggested here that this may be an unresolvable problem.

Animals↗

Patterns of dental development in Homo, Australopithecus, Pan, and Gorilla.

Smith ([1986] Nature 323:327-330) distinguished patterns of development of teeth of juvenile fossil hominids as being "more like humans" or "more like apes" based on statistical similarity to group standards. Here, this central tendency discrimination (CTD) is tested for its ability to recognize ape and human patterns of dental development in 789 subadult hominoids. Tooth development of a modern human sample (665 black southern Africans) was scored entirely by an outside investigator; pongid and fossil hominid samples (59 Pan, 50 Gorilla, and 14 fossil hominids) were scored by the author. The claim of Lampl et al. ([1993] Am. J. Phys. Anthropol. 90:113-127) that Smith's 1986 method succeeds in only 8% of human cases was not sustained. Figures for overall success of classification (87% humans, 68% apes) mask important effects of teeth sampled and age class. For humans, the power of CTD varied between 53% and 92% depending on the number and kind of teeth available--nearly that of a coin toss when data described only two nearby teeth, but quite successful with more teeth or distant teeth. For apes, only age class affected accuracy: "Infant" apes (M1 development < or = root cleft complete, unemerged) were usually classed as humans, probably because the present developmental standard for great apes is in substantial error under 3 years of age. "Juvenile" apes (M1 > or = root 1/4), however, were correctly discriminated in 87% of cases. Overall, CTD can be considered reliable (accuracy of 92% for humans and 88% for apes) when data contrast development of distant dental fields and subjects are juveniles (not infants). Restricting analysis of fossils to specimens satisfying these criteria, patterns of dental development of gracile australopithecines and Homo habilis remain classified with African apes. Those of Homo erectus and Neanderthals are classified with humans, suggesting that patterns of growth evolved substantially in the Hominidae. To standardize future research, the computer program that operationalizes CTD is now available.

Aging↗

AP endonuclease and poly(ADP-ribose) polymerase-1 interact with the same base excision repair intermediate.

Base excision repair (BER) is a defense system that protects cells from deleterious effects secondary to modified or missing DNA bases. BER is known to involve apurinic/apyrimidinic endonuclease (APE) and DNA polymerase ss (ss-pol) among other enzymes, and recent studies have suggested that poly(ADP-ribose) polymerase-1 (PARP-1) also plays a role by virtue of its binding to BER intermediates. The main role of APE is cleavage of the DNA backbone at abasic sites, and the enzyme also can catalyze 3'- to 5'-exonuclease activity at the cleaved abasic site. Photocross-linking studies with mouse embryonic fibroblast (MEF) cell extracts described here indicated that APE and PARP-1 interact with the same APE-cleaved abasic site BER intermediate. The model BER intermediate used includes a synthetic abasic site sugar, i.e. tetrahydrofuran (THF), in place of the natural deoxyribose. APE cross-linked efficiently with this intermediate, but not with a molecule lacking the 5'-THF phosphate group, and the same property was demonstrated for PARP-1. The addition of purified APE to the MEF extract reduced the amount of PARP-1 cross-linked to the BER intermediate, suggesting that APE can compete with PARP-1. APE and PARP-1 were antagonists of each other in in vitro BER related reactions on this model BER intermediate. These results suggest that PARP-1 and APE can interact with the same BER intermediate and that competition between these two proteins may influence their respective BER related functions.

Animals↗

Tacrolimus pharmacokinetics in lung transplantation: new strategies for monitoring.

BACKGROUND: Tacrolimus (TAC) dosing in lung transplantation is traditionally based on blood trough levels (C0). The best sampling strategy for the estimation of total drug exposure (area-under-the-curve [AUC]) has not been determined. METHODS: Thirty-one 12-hour pharmacokinetic profiles were studied in 15 patients (8 men and 7 women, 42.0 +/- 13 years) post-bilateral lung transplantation (7.3 +/- 3.7 months; range, 3-18 months). Twelve-hour AUC (AUC0-12) was calculated by trapezoidal rule. Relationships between individual concentration points or abbreviated kinetics (2-4 concentration points) and AUC0-12 were determined by linear regression analysis (R2; absolute prediction error [APE]). RESULTS: Pharmacokinetic profiles showed high variability, particularly in the absorption phase. AUC was 221 +/- 47.2 ng/ml (range, 156-329.3 ng/ml) at C0 10 to 15 ng/ml and was independent of TAC dose (R2 = 0.002). C0 was poorly predictive of AUC0-12 (R2 = 0.64; APE, 16.1% +/- 10.9%; range, 1.4%-37.8%). The predictive performance for AUC0-12 was highest with abbreviated kinetics using 4 (C0/C2/C3/C4: R(2) = 0.99; APE, 2.6% +/- 2.0%; range, 0.1%-7%) or 3 concentration points (C0/C2/C4: R2 = 0.98; APE, 2.6% +/- 2.1%; range, 0.1%-9.1%). Of the 2-point kinetics C2/C6 (R2 = 0.96; APE, 5.3% +/- 3.7%; range, 0.1%-12.7%), C2/C4 (R2 = 0.94, APE 6.7% +/- 4.8%; range 0.1%-14.6%) and C0/C4 (R2 = 0.94; APE 4.1% +/- 2.9%; range, 0.5%-11.4%) performed best. Single point strategies (best was C4: R2 = 0.94; APE 7.1% +/- 5.5%, range, 0.2%-24.1%) all had unacceptably high APE (range > 15%). CONCLUSION: True TAC exposure shows high variability in stable lung transplant patients and is poorly predicted by C0. Abbreviated kinetics covering at least 2 concentration points between 0 and 4 hours post-drug intake are required for an accurate estimation of AUC.

Adult↗

Ultrastructure of internal limiting membrane removed during plasmin-assisted vitrectomy from eyes with diabetic macular edema.

PURPOSE: To study the effect of autologous plasmin enzyme (APE) on the adhesion of the vitreous cortex to the internal limiting membrane (ILM) in eyes with diabetic macular edema. DESIGN: Nonrandomized, comparative, interventional case series. PARTICIPANTS: Ten eyes of 10 patients with diabetic macular edema without a posterior vitreous detachment (PVD), which were treated with APE as an adjunct to conventional pars plana vitrectomy, and 10 eyes of 9 patients without a PVD, which underwent pars plana vitrectomy without APE, were studied. METHODS: In the APE group, 0.4 IU of APE was injected into the midvitreous cavity in 9 eyes, and 0.8 IU of APE in 1 eye. Thirty minutes after plasmin injection, the eyes underwent pars plana vitrectomy with ILM peeling. All eyes in the control group had conventional vitreous surgery with ILM peeling. The removed ILMs were investigated for the presence of vitreous and for ultrastructural differences by transmission and scanning electron microscopy. MAIN OUTCOME MEASURES: The status of the vitreous and induction of a PVD during surgery, and the presence of vitreous and ultrastructural differences of the removed ILM by transmission and scanning electron microscopy. RESULTS: In APE-treated eyes, the degree of liquefaction of the vitreous was graded as high in 4 eyes. Spontaneous PVD occurred in 2 eyes, whereas core vitrectomy with a maximum vacuum of 100 mmHg induced a PVD in 2 additional eyes. In the control group, 8 eyes required suction with a maximum of 200 mmHg to induce the PVD. Scanning electron micrography of the removed ILM in the APE-treated eyes showed a smooth surface on the vitreous side in 8 eyes and only sparse collagen fibers in 2 eyes. Conversely, in the control group, dense vitreous fibers were found in 4 eyes, sparse collagen fibrils in 3 eyes, and a smooth retinal surface in 3 eyes. CONCLUSIONS: These findings indicate that APE helps separate the vitreous hyaloid from the ILM surface and may be a useful adjunct to conventional vitreous surgery for diabetic macular edema.

Adult↗

Environmental fate of alkylphenols and alkylphenol ethoxylates--a review.

Alkylphenol ethoxylates (APEs) are widely used surfactants in domestic and industrial products, which are commonly found in wastewater discharges and in sewage treatment plant (STP) effluents. Degradation of APEs in wastewater treatment plants or in the environment generates more persistent shorter-chain APEs and alkylphenols (APs) such as nonylphenol (NP), octylphenol (OP) and AP mono- to triethoxylates (NPE1, NPE2 and NPE3). There is concern that APE metabolites (NP, OP, NPE1-3) can mimic natural hormones and that the levels present in the environment may be sufficient to disrupt endocrine function in wildlife and humans. The physicochemical properties of the APE metabolites (NP, NPE1-4, OP, OPE1-4), in particular the high K(ow) values, indicate that they will partition effectively into sediments following discharge from STPs. The aqueous solubility data for the APE metabolites indicate that the concentration in water combined with the high partition coefficients will provide a significant reservoir (load) in various environmental compartments. Data from studies conducted in many regions across the world have shown significant levels in samples of every environmental compartment examined. In the US, levels of NP in air ranged from 0.01 to 81 ng/m3, with seasonal trends observed. Concentrations of APE metabolites in treated wastewater effluents in the US ranged from < 0.1 to 369 microg/l, in Spain they were between 6 and 343 microg/l and concentrations up to 330 microg/l were found in the UK. Levels in sediments reflected the high partition coefficients with concentrations reported ranging from < 0.1 to 13,700 microg/kg for sediments in the US. Fish in the UK were found to contain up to 0.8 microg/kg NP in muscle tissue. APEs degraded faster in the water column than in sediment. Aerobic conditions facilitate easier further biotransformation of APE metabolites than anaerobic conditions.

Biodegradation, Environmental↗

A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis.

Protein kinase B (PKB)/Akt reportedly plays a role in the survival and/or proliferation of cells. We identified a novel protein, which binds to PKB, using a yeast two-hybrid screening system. This association was demonstrated not only in vivo by overexpressing both proteins or by coimmunoprecipitation of the endogenous proteins, but also in vitro using glutathione S-transferase fusion proteins. Importantly, this protein specifically associates with the C terminus of PKB but not with other AGC kinases and enhances PKB phosphorylation and kinase activation without growth factor stimulation. Thus, we termed this Akt-specific binding protein APE (Akt-phosphorylation enhancer). Since APE-induced phosphorylation of PKB did not occur in cells treated with wortmannin or LY294002, APE itself is not a kinase but seems to enhance or prolong the phosphoinositide 3-kinase-dependent phosphorylation of PKB. In cells in which APE was suppressed by small interfering RNA, DNA synthesis was significantly reduced with suppression of PKB phosphorylation, suggesting a synergistic role of APE in PKB-induced proliferation. On the other hand, in cells overexpressing both PKB and APE, despite markedly increased basal phosphorylation of PKB, both DNA rereplication and subsequent Chk2 phosphorylation and apoptosis were seen, suggesting the involvement of APE in the regulation of cell cycling replication licensing. Taking these observations together, APE appears to be a novel regulator of PKB phosphorylation. Furthermore, the interaction between APE and PKB, possibly dependent on the expression levels of both proteins, may be a novel molecular mechanism leading to proliferation and/or apoptosis.

Amino Acid Sequence↗

Biomarker-based risk assessment model in acute pulmonary embolism.

AIMS: Despite growing interest in biomarkers application for risk evaluation in acute pulmonary embolism (APE), no decision-making levels have been defined. METHODS AND RESULTS: We developed a biomarker-based risk stratification in 100 consecutive, normotensive on admission, APE patients (35 males, 65 females, 62+/-18 years). On admission serum NT-proBNP and cardiac troponin T (cTnT) levels were assessed and echocardiography was performed. All-cause 40-day mortality was 15% and APE mortality was 8%. In univariable analysis, cTnT>0.07 microg/L predicted all-cause mortality, hazard ratio (HR) 9.2 (95% CI: 3.3-26.1, P<0.0001), and APE mortality, HR 18.1 (95% CI: 3.6-90.2, P=0.0004); similarly, NT-proBNP>7600 ng/L predicted all-cause and APE mortalities [HR 6.7 (95% CI: 2.4-19.0, P=0.0003) and 7.3 (95% CI: 1.7-30.6, P=0.007)]. NT-proBNP<600 ng/L indicated uncomplicated outcome. Multivariable analysis revealed that cTnT>0.07 microg/L was the most significant independent predictor, whereas NT-proBNP and systemic systolic blood pressure measured on admission and echocardiographic parameters were non-significant. APE mortality in patients with NT-proBNP> or =600 ng/L and cTnT> or =0.07 microg/L reached 33%. NT-proBNP<600 ng/L indicated group without deaths. APE mortality for patients with NT-proBNP> or =600 ng/L and cTnT<0.07 microg/L was 3.7%. Incorporation of echocardiographic data did not improve group selection. CONCLUSION: Simultaneous measurement of serum cTnT and NT-proBNP allows for precise APE prognosis. Normotensive patients on admission with cTnT> or =0.07 microg/L and NT-proBNP> or =600 ng/L are at high risk of APE mortality, whereas NTproBNP<600 ng/L indicates excellent prognosis.

Acute Disease↗

Multiple antiphospholipid tests do not increase the diagnostic yield in antiphospholipid syndrome.

The family of antiphospholipid antibodies (aPL) includes a heterogeneous population of autoantibodies whose specificity is directed against not only phospholipids, but their complex with plasma proteins. Anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) tests are widely performed to screen the aPL family which is associated with thrombotic complications in patients with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). The clinical significance of other aPL tests, including antibodies against phosphatidylserine (aPS), phosphatidylinositol (aPI), phosphatidic acid (aPA), phosphatidylcholine (aPC) and phosphatidylethanolamine (aPE), has not been established. The purpose of this study was to evaluate whether multiple aPL tests have enhanced diagnostic value for APS. We tested IgG/M/A aPS, aPI, aPA, aPC and aPE by ELISA using 10% bovine serum as blocking and sample diluent in 26 SLE patients with clinical manifestations of APS, but negative for both aCL and LA (Group 1). The results were compared with 32 SLE patients without any features of APS (Group 2) and 24 SLE patients with APS (aCL and/or LA positive) (Group 3). In Group 1, 1/26 (4%) was positive for IgA aPE, less frequent than in other groups, and none of the patients had any other aPL. In Group 2, 1/32 (3%) was positive for aPS, two (6%) for aPI, one (3%) for aPA and four (12.5%) for aPE. None was positive for aPC. In the third group, 13/24 (54%) were positive for aPS, 11 (46%) for aPI, 15 (63%) for aPA, four (17%) for aPC and seven (29%) for aPE. Since aPE was found in some patients, we extended the study, including 207 SLE patients, and tested aPE. IgG/M/A aPE was found in six (3%), 10(5%) and 21 (10%), respectively, but no association was found between aPE and any clinical features of APS. This study suggests that screening by multiple aPL tests does not increase the diagnostic yield in APS.

Adolescent↗

Lung perfusion scans and hemodynamics in acute and chronic pulmonary embolism.

UNLABELLED: To assess the relationship between pulmonary vascular obstruction and hemodynamic status in acute pulmonary embolism (APE) and in chronic thromboembolic pulmonary hypertension (CTEPH), perfusion lung scan and hemodynamic measurements were obtained in 31 consecutive patients with APE and in 45 with CTEPH. METHODS: Lung scans were scored independently by two experience observers who determined the percentage of vascular obstruction (PVOs). Mean pulmonary artery pressure (PAP) and total pulmonary resistance (TPR) were obtained during right heart catheterization. In patients with APE, measurements were recorded within a 1-hr interval before and 12 hours after thrombolysis. This yielded 62 paired PVOs values with concomitant PAP and TPR measurements. In patients with CTEPH, data were recorded within a 3-day interval. RESULTS: Mean PVOs (%) values were similar in APE and CTEPH patients (59 +/- 13 vs. 58 +/- 15), whereas PAP and TPR were significantly higher in CTEPH patients (51 +/- 17 mmHg and 23 +/- 11 U/m2, respectively) than in APE patients (23 +/- 8 mmHg and 9 +/- 5 U/m2, respectively, p < 0.001). In APE patients, significant hyperbolic correlations were found linking PVOs with PAP and TPR (r = 0.75, p < 0.01 for PAP; r = 0.71, p < 0.01 for TPR). In CTEPH, there were no significant correlations between PVOs and PAP or TPR. For the same level of PVOs, patients with CTEPH had higher PAP and TPR value than patients with APE. CONCLUSION: In APE without prior cardiopulmonary disease, increases in PAP and TPR are correlated in a nonlinear fashion with the degree of pulmonary vascular obstruction as assessed by lung scanning. In CTEPH patients, the higher PAP and TPR values as compared to APE patients with comparable degrees of PVOs are consistent with previous reports that pulmonary hypertension in CTEPH is due not only to the obstruction of proximal pulmonary arteries but also to remodeling of small distal arteries in nonoccluded areas.

Acute Disease↗

Long-term effects of acute pulmonary embolism on echocardiographic Doppler indices and functional capacity.

BACKGROUND AND HYPOTHESIS: Hemodynamic and functional consequences of acute pulmonary embolism (APE) are believed to be reversible with antithrombotic treatment. To verify this hypothesis, we reassessed our patients at least 1 year after an episode of APE. METHODS: We compared echo Doppler indices and 6-min walking test parameters (6-MWT) of 36 patients (13 men, 23 women, age 66 +/- 11 years), studied on average 3.1 +/- 2.2 years after an acute episode of pharmacologically treated massive or submassive APE, with data of 30 age-matched subjects (12 men, 18 women, age 67 +/- 12 years). RESULTS: At least 1 year after APE, right ventricular (RV) diameter remained increased in patients compared with controls (27 +/- 2 vs. 23 +/- 2 mm, p<0.001). Also, acceleration time of pulmonary ejection (AcT) was markedly shorter (97 +/- 19 vs. 123 +/- 19 ms, p<0.001) and the diameter of the pulmonary trunk was significantly larger in patients than in controls (21 +/- 2.6 vs. 18 +/- 2.2, p<0.001). Although the mean value of the tricuspid valve peak systolic gradient (TVPG) in the APE group at follow-up was similar to that in controls, TVPG>30 mmHg was recorded in three patients with APE (8.3%). There was no difference in the distance of 6-MWT between both groups; however, the mean desaturation after 6-MWT was higher in the APE group than in controls (3.04 +/- 2.08 vs. 1.45 +/- 0.69%, p=0.0005). CONCLUSIONS: Pharmacologic treatment of acute pulmonary embolism does not prevent mild persistent changes in morphology and function of the cardiovascular system. Despite normalization of pulmonary artery systolic pressure and similar exercise capacity, survivors of APE present signs suggesting RV dysfunction and/or its disturbed coupling to the pulmonary arterial bed, as well as ventilation to perfusion mismatch at exertion persisting long after the acute embolic episode.

Acute Disease↗

Prediction of aortic peak enhancement in monophasic contrast injection protocols at multidetector CT: phantom and patient studies.

PURPOSE: The aim of this study was to investigate whether it is possible to predict aortic peak enhancement (APE) from the contrast dose and injection rate. MATERIALS AND METHODS: We first undertook an experimental study using a flow phantom that simulates the human circulation. We delivered 90-150 ml of iomeprol-350 at various injection rates and measured the APE values of the simulated aorta. In our clinical study we randomized 20 patients into four groups. In groups A, B, and C the iodine dose per kilogram of body weight (BW) ranged from 450 to 600 mg, and the injection duration was fixed at 30 s; group D received 450 mg/kg over 25 s. We then measured APE in all patients at the whole aorta, averaged the three highest values, and took the result as APE. RESULTS: In the phantom study, the decision coefficient for the best-fit equation obtained by multiple regression analysis of the relation between the iodine dose and injection rate and the simulated APE was high (0.93). In the patient study, the predicted APE values almost corresponded with the averaged APE values when we applied the fitness equation. CONCLUSION: Using our fitness equation, APE on contrast-enhanced computed tomography can be predicted from the iodine dose and the contrast injection rate per patient weight.

Adult↗

Intrasurgical plasmin enzyme in diabetic macular edema.

PURPOSE: To evaluate in a prospective study the efficacy of intrasurgical autologous plasmin enzyme (APE) in producing posterior vitreous detachment. DESIGN: Consecutive, interventional case series. METHODS: A group of 12 eyes of 11 patients with diabetic macular edema secondary to posterior vitreous cortex contraction was considered. A quantity of 0.1- to 0.2-ml containing 0.8 to 1.2 IU of APE prepared by our Coagulation Service was injected into the vitreous body 25 minutes before surgery. The efficacy of the APE was subjectively evaluated. A control group of 10 eyes with the same clinical characteristics underwent the same surgery without APE injection. Complete eye examinations, including optical coherence tomography, were performed on all patients before surgery and during the 1-year follow-up period. RESULTS: During surgery in the APE-treated group, the posterior vitreous cortex was judged adherent in three cases, partially detached in six cases, and totally detached in three cases. In two cases a complete collapse of the vitreous body was observed. During surgery in the non-APE-treated group, the posterior vitreous cortex was judged still adherent in nine of 10 eyes and partially detached in 1 eye. Comparing the postoperative results between the APE-treated group and the non-APE-treated group, we found no significant differences in final postoperative retinal thickness (P = .2552), whereas we found a significant difference in final visual acuity (P = .0121). CONCLUSIONS: Autologous plasmin enzyme was useful in inducing a pharmacologic posterior vitreous detachment and in facilitating surgery. It did not seem to interfere with the final retinal thickness, and it ameliorates the final visual acuity.

Aged↗