Anti-Ro/SS-A and anti-La/SS-B antibodies associated with cardiac involvement in childhood systemic lupus erythematosus

OBJECTIVES—To determine the frequency and type of cardiac manifestations in children with systemic lupus erythematosus (SLE) and investigate whether cardiac involvement of SLE in children was associated with any autoantibody pattern.
METHODS—Retrospective analysis of the medical records of all children with SLE (31 patients) seen between January 1984 and January 1994 by the paediatric rheumatology service at Children's Hospital in New Orleans. All patients satisfied the American College of Rheumatology criteria for the diagnosis of SLE. Paediatric SLE patients with cardiac manifestations based on echocardiogram were identified. Autoantibody tests at diagnosis were identified retrospectively by chart review, and the correlation between autoantibodies and cardiac involvement was analysed using the two tailed Fisher's exact test.
RESULTS—Thirteen (42%) of 31 SLE patients had cardiac manifestations of SLE. Seven (22%) had pericarditis without myocarditis, five (16%) had pericarditis and myocarditis, and one (3%) had myocarditis without pericarditis. Two patients (6%) with pericarditis had cardiac tamponade. Cardiac manifestations of SLE usually occurred at the time of diagnosis or within six months. Anti-Ro/SS-A antibodies were present in serum samples of nine of 11 (82%) patients with cardiac involvement and in five of 15 (33%) without cardiac involvement (p=0.02). Anti-La/SS-B antibodies were present in serum samples of six of 10 (60%) patients with cardiac involvement and two of 15 (13%) without cardiac involvement (p=0.03). Anti-Sm and anti-RNP antibodies showed no correlation with the presence of cardiac disease.
CONCLUSIONS—Cardiac involvement in our paediatric SLE population was frequently found and correlated significantly with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies.

     

The regulation of hemopoiesis in long-term bone marrow cultures. II. Stimulation and inhibition of stem cell proliferation

The isolation of a DNA synthesis inhibitor (NBME fraction IV) and stimulator (RBME fraction III) specific for the hemopoietic stem cell (CFU-s) from freshly isolated normal adult and regenerating murine bone marrow, respectively, has been well documented. We have utilized long- term liquid bone marrow cultures in a further analysis of the role of these factors in the regulation of CFU-s proliferation. Our results show that shortly after feeding, at a time when the cultured CFU-s are actively proliferating, high levels of the hemopoietic stem cell proliferation stimulator fraction III can be isolated from the culture medium. In contrast, the presence of essentially noncycling CFU-s found in cultures fed 8-10 days previously correlates with high levels of the hemopoietic stem cell inhibitor fraction IV. These results suggest that a certain balance between these factors determines CFU-s proliferation in the long-term cultures. In support of this, DNA synthesis in actively cycling CFU-s in the long-term cultures is inhibited for at least 3 days by the addition of excess NBME fraction IV (inhibitor). Furthermore, DNA synthesis in noncycling cultured CFU-s is stimulated for at least 5 days by the addition of RBME fraction III (stimulator).     

Advanced glycation end products contribute to amyloidosis in Alzheimer disease.

Alzheimer disease (AD) is characterized by deposits of an aggregated 42-amino-acid beta-amyloid peptide (beta AP) in the brain and cerebrovasculature. After a concentration-dependent lag period during in vitro incubations, soluble preparations of synthetic beta AP slowly form fibrillar aggregates that resemble natural amyloid and are measurable by sedimentation and thioflavin T-based fluorescence. Aggregation of soluble beta AP in these in vitro assays is enhanced by addition of small amounts of pre-aggregated beta-amyloid "seed" material. We also have prepared these seeds by using a naturally occurring reaction between glucose and protein amino groups resulting in the formation of advanced "glycosylation" end products (AGEs) which chemically crosslink proteins. AGE-modified beta AP-nucleation seeds further accelerated aggregation of soluble beta AP compared to non-modified "seed" material. Over time, nonenzymatic advanced glycation also results in the gradual accumulation of a set of posttranslational covalent adducts on long-lived proteins in vivo. In a standardized competitive ELISA, plaque fractions of AD brains were found to contain about 3-fold more AGE adducts per mg of protein than preparations from healthy, age-matched controls. These results suggest that the in vivo half-life of beta-amyloid is prolonged in AD, resulting in greater accumulation of AGE modifications which in turn may act to promote accumulation of additional amyloid.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.     

Treatment options for post-catheterisation femoral pseudoaneurysm closure

BACKGROUND: Femoral artery pseudoaneurysm (FAP) complicates from 1% to 9% of all coronary angiography procedures and contributes to extended hospitalisation as well as patient discomfort. AIM: To compare three main methods of FAP closure which are used nowadays. METHODS: Seventy-five subjects (38 females, 37 males, mean age 60.8+/-10.4 years) with post-catheterisation FAP were studied. The results of three methods of FAP closure--surgical, local compression and thrombin injection--were compared. RESULTS: Between September 2000 and July 2001, fourteen patients developed FAP; in 9 (64%) patients FAP was closed with repeated prolonged compression whereas the remaining 5 (36%) patients required surgical closure of compression-resistant FAP. We observed that FAPs with longer neck (>10 mm) and primary signs of partial spontaneous coagulation were more prone to self-closure as compared to FAPs with short neck and no signs of perimural coagulation (p=0.01). Since July 2001, we introduced ultrasound-guided thrombin injection into FAP sack. The protocol included attempt of closing FAP with probe compression and compression dressing put overnight, and, if unsuccessful, followed by a quick injection of 2 ml of thrombin solution (400-3200 U), guided by ultrasound. During this period, we identified 61 patients with FAP. Out of this group, 5 (8.2%) subjects were referred for surgery without any attempt of thrombin-injection, in 16 (26.2%) patients FAP was closed with probe compression and dressing put overnight, and in the remaining 40 (65.6%) subjects ultrasound-guided thrombin-injection was performed. Thrombin injection into FAP sack caused closure of its cavity and neck in all patients, however, five patients required additional thrombin injection during the same session, and 2 (5.0%) patients--during the next procedure. No peri-procedural complications were observed. The duration of hospital stay shortened from a mean of 26.6+/-14.5 days in surgically treated patients to 7.9+/-6.7 in those in whom FAPs were closed with compression, and to 4.6+/-2.6 days in those treated with thrombin (p<0.001). During a mean follow-up of 11+/-8.1 months, we re-examined 32 (80.0%) patients in whom FAP was closed with thrombin injection. No long-term thrombotic or embolic complications were observed. However, in 2 (6.3%) patients FAP cavity did not undergo complete resorption after 6 and 12 months of follow-up. CONCLUSIONS: Thrombin-induced closure of femoral pseudoaneurysm is a quick, safe and effective method, shortening hospitalisation time. In our Department this procedure replaced the prolonged and painful compression method.     

Negative self-appraisals in treatment-seeking survivors of motor vehicle accidents

Recent cognitive models stress the impact that negative appraisals have on the maintenance of posttraumatic stress disorder (PTSD). The aim of this study was to investigate the role of posttraumatic negative cognitions in 110 survivors of motor vehicle accidents (MVAs) and to examine the effect of cognitive-behavioral treatment on negative appraisals in a sample of 42 patients with full or sub-syndromal PTSD. We investigated whether posttraumatic negative cognitions predicted PTSD diagnosis and symptom severity, and whether treatment-related changes in negative appraisals were associated with PTSD symptom reduction. Negative posttraumatic cognitions were significantly associated with PTSD diagnosis and severity, and explained 54% of the variance of the PTSD severity. Furthermore, treatment-related reductions in negative appraisals about the self were highly associated with PTSD-symptom-reduction. Our results raise question about whether there are factors that make the self more vulnerable in some people but not in others.     

Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody

A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.