Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, double-blind, placebo-controlled trial

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials. (AU)

Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

Rivaroxaban, Aspirin, or Both to Prevent Early Coronary Bypass Graft Occlusion: The COMPASS-CABG Study.

BACKGROUND: Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. OBJECTIVES: This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. METHODS: The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. RESULTS: The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. CONCLUSIONS: The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424).

Somatic complaints among pregnant women cared for in obstetrics: normal pregnancy or depressive and anxiety symptom amplification revisited?

Despite the extensive research documenting the significance of medically unexplained somatic symptoms in primary care patients, few studies have examined somatic symptoms as a predictor of depressive and anxiety disorders among pregnant women cared for in Obstetrics. We utilized the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PHQ) to assess current depressive and anxiety disorders and self-reported somatic symptoms among 186 women receiving prenatal care. We examined the bivariate relationships between depressive and anxiety disorders and mean number of somatic symptoms. Linear regression analyses assessed the unique association between maternal depression, anxiety and somatic symptoms, while controlling for selected demographics and maternal medical risk. Twenty three percent (N=43) of women met screening criteria for depressive and/or anxiety disorders. Women with depression and/or anxiety were significantly more likely to report somatic symptoms (mean=7.1, SD=2.6) compared to women without depression or anxiety (mean=5.0, SD=2.6) [t(df)=4.54(184), P<.001]. This association persisted in multivariate models. Our findings suggest that antenatal depressive and anxiety disorders are associated with an amplification of physical symptoms of pregnancy. Eliciting and tracking somatic symptoms during prenatal visits could potentially improve detection of depressive and anxiety disorders in the obstetrical sector.

Posttraumatic concerns: a patient-centered approach to outcome assessment after traumatic physical injury.

BACKGROUND: Approximately 2.5 million Americans are admitted to the hospital after traumatic physical injury each year. Few investigations have elicited patients' perspectives regarding posttraumatic outcomes. OBJECTIVE: To identify and categorize physically injured trauma survivors' posttraumatic concerns. RESEARCH DESIGN: Prospective longitudinal investigation; trauma survivors were interviewed during the post-injury hospitalization and again 1, 4, and 12 months after the trauma. SUBJECTS: Ninety-seven, randomly selected, English speaking, hospitalized survivors of motor vehicle-crashes or assaults. MEASURES: At the end of each interview patients were asked, "Of all the things that have happened to you since you were injured, what concerns you the most?" Using an iterative process and working by consensus, investigators categorized patient concerns in content domains. Concern domains were then compared with established measures of posttraumatic stress disorder (PTSD) symptoms and limitations in physical functioning. RESULTS: Seven categories of posttraumatic concerns were identified. During the course of the year, 73% of patients expressed physical health concerns, 58% psychological concerns, 53% work and finance concerns, 40% social concerns, 10% legal concerns, 10% medical concerns, and 20% uncodable concerns. Rater agreement on concern categorization was substantial (kappa = 0.72). The mean number of concerns expressed per patient gradually decreased over time (1 month mean = 1.51; 12 month mean = 1.26) and resembled the trajectories of PTSD symptoms and functional limitations. CONCLUSIONS: The concerns of physically injured trauma survivors are readily elicited and followed up during the course of the year after injury. Open-ended inquiry regarding posttraumatic concerns may complement standardized outcome assessments by identifying and contextualizing the outcomes of greatest importance to patients.

Trimethylamine oxide counteracts effects of hydrostatic pressure on proteins of deep-sea teleosts.

In shallow marine teleost fishes, the osmolyte trimethylamine oxide (TMAO) is typically found at <70 mmol/kg wet weight. Recently we found deep-sea teleosts have up to 288 mmol/kg, increasing in the order shallow < bathyal < abyssal. We hypothesized that this protein stabilizer counteracts inhibition of proteins by hydrostatic pressure, and showed that, for lactate dehydrogenases (LDH), 250 mM TMAO fully offset an increase in NADH K(m) at physiological pressure, and partly reversed pressure-enhanced losses of activity at supranormal pressures. In this study, we examined other effects of pressure and TMAO on proteins of teleosts that live from 2000-5000 m (200-500 atmospheres [atm]). First, for LDH from a grenadier (Coryphaenoides leptolepis) at 500 atm for 8 hr, there was a significant 15% loss in activity (P < 0.05 relative to 1 atm control) that was reduced with 250 mM TMAO to an insignificant loss. Second, for pyruvate kinase from a morid cod (Antimora microlepis) at 200 atm, there was 73% increase in ADP K(m) without TMAO (P < 0.01 relative to K(m) at 1 atm) but only a 29% increase with 300 mM TMAO. Third, for G-actin from a grenadier (C. armatus) at 500 atm for 16 hr, there was a significant reduction of F-actin polymerization (P < 0.01 compared to polymerization at 1 atm) that was fully counteracted by 250 mM TMAO, but was unchanged in 250 mM glycine. These findings support the hypothesis. J. Exp. Zool. 289:172-176, 2001.

Circumventing complement C3 interference in the analysis of carbohydrate-deficient transferrin in fresh serum.

A method for preventing interference by the glycoprotein complement C3 and its beta-globulin split products in the capillary electrophoretic analysis of carbohydrate-deficient transferrin was developed. Inulin was used to activate the alternate complement pathway and convert native C3 into various degradation products whose electrophoretic mobility no longer coincides with the transferrin glycoforms. Capillary electrophoresis and zone electrophoresis on agarose gel were used to monitor reaction conditions for alternate complement pathway activation. Incubation of 50 microL of fresh serum with 180 microL of a 50 mg/mL inulin slurry for 12 h removed the native C3 peak from the beta region. Inulin treatment did not affect electrophoretic behavior of other beta-globulins, including transferrin. Altering the electrophoretic behavior of complement C3, by treating fresh serum with inulin, permits rapid capillary electrophoresis evaluation of carbohydrate-deficient transferrin glycoforms.

Factitious hearing loss and otorrhea in an adolescent boy.

Asialo, or beta(2), transferrin occurs in cerebrospinal fluid and a few other body fluids, e.g., perilymph and aqueous humor. It is used clinically as a marker protein to detect CSF otorrhea and rhinorrhea. Asialo-transferrin is separated from sialylated serum transferrin glycoforms by electrophoresis and detected by Western blotting. Potential pitfalls in interpreting Western blots occur when other transferrin isoforms approximate the migratory behavior of asialo-transferrin. In the present report an adolescent boy was seen by an otolaryngologist for otorrhea and acute hearing loss. The otorrhea fluid, subsequently identified as saliva, contained a transferrin isoform with electrophoretic mobility similar to that of asialo-transferrin.

Serum protein immunogenicity: implications for liver xenografting.

The objectives of this study were threefold: (i) assess immunogenicity of donor plasma proteins following hepatic xenotransplantation, (ii) identify potential immunogens, and (iii) consider the implications of antibody formation against these plasma proteins in xenograft survival. We studied liver and heart xenografts in a concordant combination, hamster to rat. All grafts were examined at necropsy for evidence of rat immunoglobulin G (IgG) deposition. Cardiac xenografts were placed in recipients who had, or had not, been sensitized with hamster serum. Hepatic xenografts were placed in naive recipients to see if antibodies to hamster serum proteins could be eluted from the rejecting organ. Sera of immunized rats were examined for the presence of anti-hamster antibodies by immunoelectrophoresis and by Western blotting following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of hamster serum. Antibodies in sera of immunized rats were compared with those eluted from rejecting livers. Candidate antigens were identified by tandem mass spectrometry, sequence analysis, and reference to protein databases. Results showed that sera of immunized rats recognized a minimum of four different antigens in hamster serum by immunoelectrophoresis, and a minimum of seven by the more sensitive SDS-PAGE Western blot. IgG eluted from rejecting livers bound three of seven candidate antigens recognized by sera of the immunized animals. Sequence analysis searches revealed proteinase inhibitors in each of the three SDS-PAGE bands common to the above samples. All of these candidate proteinase inhibitor immunogens share a common catabolic fate, uptake via the lipoprotein-related protein (LRP/alpha 2-macroglobulin receptor (CD91). Sensitization to hamster serum proteins hastened cardiac xenograft rejection in 30-50% of recipients (depending on sensitization protocol). Vascular deposition of rat IgG occurred in all rejecting xenografts. Antibody binding to proteinase inhibitors could disturb their functional activity and contribute to the pathogenesis of delayed xenograft rejection.

Adequacy of prenatal care among women with psychiatric diagnoses giving birth in California in 1994 and 1995.

OBJECTIVE: Although poor prenatal care is detrimental to maternal and infant health, few studies have assessed the adequacy of prenatal care among women with psychiatric diagnoses. This investigation examined the association between chart-recorded psychiatric and substance use diagnoses at the time of delivery and adequacy of prenatal care among all women delivering babies in California hospitals during 1994 and 1995. METHODS: The authors undertook an archival analysis of data from the California Health Information for Policy Project (CHIPP), which consists of linked hospital discharge and birth certificate data for 1,094,178 deliveries in 1994 and 1995. The associations between International Classification of Diseases, 9th Revision, Clinical Modification psychiatric and substance abuse diagnoses and level of prenatal care were examined. Logistic regression analyses were conducted to assess the association between maternal diagnostic category and inadequate prenatal care while controlling for payment source, age, education, race, marital status, and parity (previous births). RESULTS: Women who received psychiatric and substance use diagnoses demonstrated significantly increased risk of inadequate prenatal care compared with women without those diagnoses. CONCLUSIONS: Psychiatric diagnoses were associated with an increased risk of inadequate prenatal care; the association between psychiatric and substance use diagnoses and poor prenatal care persisted even after the analysis controlled for known risk factors. Future investigations will need to elucidate the processes of prenatal care for women with psychiatric disorders so that preventive interventions can be developed.

Rapid onset monoclonal gammopathy in cutaneous lupus erythematosus: interference with complement C3 and C4 measurement.

Accurate nephelometric immunoassay requires both the analyte and the calibration standard to have the same molecular mass. Alteration in the size of the analyte can affect light scatter and yield erroneous results. We report a case where an autoantibody, a monoclonal IgM with immunoconglutinin activity, interfered with the nephelometric quantitation of plasma complement components C3 and C4.

Chart-recorded psychiatric diagnoses in women giving birth in California in 1992.

OBJECTIVE: Although major advances have been made in the diagnosis and treatment of mental disorders in primary care, few population-based investigations have focused on the obstetrical sector. This study examines the occurrence of chart-recorded psychiatric discharge diagnoses among all women delivering in California hospitals in 1992. METHOD: The authors undertook an archival analysis of the California Health Information for Policy Project data set, which consists of linked hospital discharge and birth certificate data for 580,282 deliveries. Frequencies of ICD-9 psychiatric diagnoses were ascertained. RESULTS: Among all women delivering, 1.5% received psychiatric or substance use diagnoses. Of diagnoses recorded, 75% were substance use disorders, 21% were classified generically as "mental disorder of pregnancy," and other psychiatric disorders accounted for 4%. CONCLUSIONS: The occurrence of psychiatric diagnoses in these women is markedly lower than expected, suggesting an underreporting of psychiatric disorders at delivery. Further investigations into the detection of mental disorders in the obstetrical sector are needed.

Beta-2 transferrin assay in the identification of perilymph.

HYPOTHESIS: Western blot assay for beta-2 transferrin protein is a clinically useful method for the detection of human perilymph and should be used for the diagnosis of perilymph fistulas (PLFs). BACKGROUND: Considerable controversy exists regarding the diagnosis of PLF. Recent studies suggest that the detection of beta-2 transferrin protein may be useful in the identification of perilymph. METHODS: To evaluate the usefulness of the beta-2 transferrin assay for identifying human perilymph, paired perilymph samples and negative controls were collected on Gelfoam pledgets from 20 patients who had surgery that opened the inner ear. Blinded immunoelectrophoretic assay (Western blot) for beta-2 transferrin was performed on each specimen. RESULTS: Only one (5%) of the known perilymph samples and none of the control specimens were definitely positive for beta-2 transferrin. Combined with historical data, this assay has 29% sensitivity, 100% specificity, 100% positive predictive value, and 31% negative predictive value. CONCLUSIONS: These findings suggest that the beta-2 transferrin protein assay may not be a reliable method for detecting human perilymph when performed using this technique.

High contents of trimethylamine oxide correlating with depth in deep-sea teleost fishes, skates, and decapod crustaceans.

In muscles of shallow-living marine animals, the osmolyte trimethylamine N-oxide (TMAO) is reportedly found (in millimoles of TMAO per kilogram of tissue wet weight) at 30-90 in shrimp, 5-50 in crabs, 61-181 in skates, and 10-70 in most teleost fish. Recently our laboratory reported higher levels (83-211 mmol/kg), correlating with habitat depth, in deep-sea gadiform teleosts. We now report the same trend in muscles of other animals, collected off the coast of Oregon from bathyal (1800-2000 m) and abyssal plain (2850 m) sites. TMAO contents (mmol/kg +/- SD) were as follows: zoarcid teleosts, 103 +/- 9 (bathyal) and 197 +/- 2 (abyssal); scorpaenid teleosts, 32 +/- 0 (shallow) and 141 +/- 16 (bathyal); rajid skates, 215 +/- 13 (bathyal) and 244 +/- 23 (abyssal); caridean shrimp, 76 +/- 16 (shallow), 203 +/- 35 (bathyal), and 299 +/- 28 (abyssal); Chionoecetes crabs, 22 +/- 2 (shallow) and 164 +/- 15 (bathyal). Deep squid, clams, and anemones also had higher contents than shallow species. Osmoconformers showed compensation between TMAO and other osmolytes. Urea contents (typically 300 mmol/kg in shallow elasmobranchs) in skates were 214 +/- 5 (bathyal) and 136 +/- 9 (abyssal). Glycine contents in shrimp were 188 +/- 17 (shallow) and 52 +/- 20 (abyssal). High TMAO contents may reflect diet, reduce osmoregulatory costs, increase buoyancy, or counteract destabilization of proteins by pressure.

Early recipient-donor switch of the complement type after liver xenotransplantation.

Liver transplantation is an immunological peculiarity with respect to the resistance of the graft to humoral rejection. We undertook a kinetic analysis of molecules involved in humoral rejection for a period of one week following xenografting in the hamster to rat model system. A complement-dependent lymphocytotoxicity test (CDC) was used to detect anti-donor antibodies in the recipient rats. Complement was studied by two methods. Function of the classical complement pathway was evaluated with a hemolytic assay, and C3 was measured by radial immunodiffusion. Conversion of the major plasma proteins from recipient to donor profile was studied by zone electrophoresis on agarose. CDC showed antibody titers rose during the first week post-transplantation, and they were of complement-activating isotypes. Zone electrophoresis showed almost complete replacement of rat C3 by hamster C3 within 72 hours. Hemolytic assay of complement on day 6 post-transplant showed serum of the xenograft recipients could lyse erythrocytes sensitized with rat antibody with 80% of efficiency of normal rat serum. Our data show the effector molecules for humoral rejection, rat antibodies with anti-hamster specificity and a functional complement cascade, were present within the first week following transplantation. Rapid conversion of serum complement to hamster proteins maintains compatibility with the species-specific membrane inhibitors of complement activation expressed by the xenografted hepatocytes, and could limit complement-mediated damage.

Hepatic hyperplasia and cancer in rats: metabolic alterations associated with cell growth.

BACKGROUND & AIMS: We showed previously that the peroxisome proliferators di(2-ethylhexyl)phthalate (DEHP), clofibrate, and 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyl)acetamide (BR931) alter hepatic sex steroid metabolism and receptor expression during induction of hepatic hyperplasia and hepatocellular carcinoma (HCC) in rats. The aim of this study was to identify metabolic changes associated with cell growth during hyperplasia and HCC. METHODS: Hepatic hyperplasia was induced in male rats by a diet containing DEHP and clofibrate for 3-60 days. HCC was induced by feeding a diet containing BR931, a more potent hepatocarcinogen, for 10 months. RESULTS: Cholesterol biosynthesis was depressed in hyperplastic livers but increased in HCC. Glucose-6-phosphate dehydrogenase (G6PD) activity was inhibited in hyperplastic liver as well as in HCC, whereas malic enzyme activity increased severalfold. Protein and messenger RNA (mRNA) levels for both G6PD and malic enzyme increased in hyperplastic livers and HCC. mRNA levels for 3-hydroxy-3-methylglutaryl-coenzyme A reductase decreased in hyperplasia and increased in HCC, whereas low-density lipoprotein receptor mRNA increased in hyperplasia and decreased in HCC. CONCLUSIONS: Neoplastic cells acquire a growth advantage by their capacity to synthesize cholesterol and obtain reduced nicotinamide adenine dinucleotide phosphate by the malic enzyme pathway when G6PD activity is inhibited by peroxisome proliferators.

Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity.

OBJECTIVE: To determine if measurement of serum complement split products (C4d, Bb, C5b-9) is better than conventional C3 and C4 measurements in distinguishing patients with varying degrees of lupus disease activity, and to determine if the presence of C3d in urine is helpful in distinguishing lupus patients with from those without early lupus nephritis. METHODS: Lupus disease activity was prospectively determined at 3 consecutive visits an average of 4 months apart, using the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and physician global assessment (PGA). Blood samples were evaluated for the presence of C4d, Bb, and C5b-9 by quantitative microassay plate enzyme immunoassay at each patient visit. We characterized urinary excretion of C3 fragments (with attention to C3d) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blotting. RESULTS: Thirty-one SLE patients were enrolled in the study. The mean SLAM score and the mean SLEDAI score each correlated well with the PGA at all 3 visits. A SLAM score of 6 and a SLEDAI score of 4 had the best overall sensitivity and specificity for predicting moderate-to-severe disease activity by PGA (100% and 73%, respectively, for the SLAM and 86% and 94%, respectively, for the SLEDAI). Serum C4d and Bb were more sensitive indicators of current moderate-to-severe lupus disease activity at all 3 visits than were serum C5b-9, C3, and C4. C3 and C4 were more specific indicators of moderate-to-severe disease activity. Serum C4d and Bb were more sensitive at predicting moderate-to-severe disease activity at subsequent visits than were C5b-9, C3, and C4. Urine C3d was better than C3, plasma C4d, Bb, C5b-9 and anti-double-stranded DNA antibody in distinguishing patients with from those without acute lupus nephritis (P = 0.02). CONCLUSION: C4d and Bb are sensitive indicators of moderate-to-severe lupus disease activity and may be most helpful in situations where conventional measurements are not, such as in lupus patients whose C3 and C4 levels remain normal despite evidence of clinical disease activity. It appears from this study that detection of urine C3d may be a simple way of measuring complement activation in the setting of lupus renal disease. The availability of instruments for clinical disease activity measurement such as the SLAM and the SLEDAI may enable more consistent definition of lupus disease activity and may thus provide a means for better examining the role of complement activation products in predicting lupus disease activity in larger patient populations.

Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation: studies toward further defining their significance.

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretransplantation and posttransplantation immunologic monitoring of anti-donor IgG lymphocytotoxic antibody titers, total hemolytic complement activity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody state in clinical hepatic transplantation. Ten contemporaneous liver transplant recipients whose crossmatch results were negative and who experienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day after transplantation and during the 1 month follow-up remained negative in 14 of 22 (64%) sensitized recipients, most of whom had relatively low (< or = 1:16) anti-donor IgG antibody titers before transplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity that reached normal levels within 1 week. A strong negative correlation between prothrombin time (PT) and CH100 activity in these groups of patients suggested that changes in CH100 activity (P < .0005) were tightly linked to liver synthetic function. In contrast, the crossmatch test results remained positive after transplantation in 8 of 22 (36%) sensitized recipients, all of whom had relatively high (> 1:32 to 1024) pretransplantation titers of anti-donor IgG antibodies. After transplantation these patients developed a syndrome that was characterized by decreased CH100 activity and increased CIC compared with pretransplantation levels and refractory thrombocytopenia that was associated with a 50% allograft failure rate because of biopsy-proven humoral and acute (cellular) rejection.(ABSTRACT TRUNCATED AT 250 WORDS)