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Biomedical subjects

J Schwab

Publications and source records attributed to J Schwab.

At least 37 records · Page 2Linked to original sources

[Churg-Strauss syndrome with right ventricular tumor].

HISTORY AND CLINICAL FINDINGS: A 47-year-old woman was admitted because of diarrhoea (3-5 stools daily) for 9 days, weakness for 3 weeks and painful wrist swelling, arthralgia and hyperesthesia over the medial aspect of the right thigh for 6 weeks. For 6 years she had been treated for asthma. Two operation had been performed for chronic sinusitis. ADMISSION FINDINGS AND INVESTIGATIONS: There was marked eosinophilia (5889/microliter) and thrombocytopenia (96,000/microliter), markedly increased serological inflammatory parameters and a raised total IgE level (134 IU/ml). The chest radiogram showed pulmonary infiltrates and bone marrow biopsy indicated eosinophilia. Echocardiography revealed a mass, 3 x 8 cm, in the ventral wall of the right ventricle with extension into the outflow tract. DIAGNOSIS, TREATMENT AND COURSE: These findings met the criteria of the American College of Rheumatology for Churg-Strauss syndrome (CSS). On methylprednisolone (1 mg/kg daily) the eosinophil and platelet counts became normal within 5 days and erythrocyte sedimentation rate and the level of C-reactive protein fell. Under cardiopulmonary bypass the tumour was removed, the tricuspid valve replaced, and the right ventricle reconstructed. Histology of the mass revealed it to be an organized thrombus. CONCLUSION: The relationship between the thrombus formation and CSS is unclear. Hypercoagulability connected with the inflammatory process may have played a part in the pathogenesis.

Anti-Inflammatory Agents↗

The effect of sex hormone replacement therapy on behavior problems and moods in adolescents with delayed puberty.

OBJECTIVE: The objective of this clinical study was to determine the effects of sex steroids on behavior and mood in adolescents with hypogonadism. STUDY DESIGN: The experimental design consisted of a randomized, double-blind, placebo-controlled, crossover trial lasting for 21 months. The study group consisted of 39 boys and 16 girls recruited from a pediatric endocrine clinic for delayed puberty. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks, alternating with placebo, at 3 dose levels approximating early, middle, and late pubertal amounts. The Child Behavior Checklist, Youth Self Report, Differential Emotion Scale, and Daily Mood Diary were administered after each placebo and treatment period to ascertain the effect of sex steroids on self- and parent-reported behavior problems and moods. RESULTS: The data demonstrated only one significant treatment effect, namely, an increase in withdrawn behavior problems during administration of low-dose estrogen in girls. There were no consistent sex differences. CONCLUSION: These results demonstrate that administered testosterone or estrogen has minimal effects on behavior problems or mood in adolescents.

Adolescent↗

[The diagnostic accuracy and therapeutic relevance of CT arthrography and MR arthrography of the shoulder].

PURPOSE: In glenohumeral instability, CT arthrography and MR arthrography of the shoulder joint were compared to assess accuracy in diagnosis of labral lesions and other internal derangements of the joint, and to evaluate relevance of both imaging methods for therapy. METHODS: 38 patients with symptoms of shoulder instability were examined clinically, arthrographically with CT and MRI, and arthroscopically. Arthrography with CT and MRI was performed in a double-contrast technique after single puncture and simultaneous injection of the contrast agents for both imaging methods. Type and extent of lesions on arthrographic imaging were criteria for planning therapy to a conservative, sole arthroscopic, or open surgical approach. RESULTS: Sensitivity in diagnosis of labral lesion (26 defects) was 85% in CT, 88% in MRI and 100% if both methods were used. Full-thickness tears of the rotator cuff were visualised in CT in 73%, and in MRI in 100%. Diagnostic accuracy increased from partial to complete to total defects. An open surgical approach was correctly predicted on MRI in 90% and on CT in 71%. A sole arthroscopic therapy was correctly foreseen on both arthrographic techniques in only 38% due to difficulties to assess glenohumeral ligaments. CONCLUSIONS: CT arthrography and MR arthrography were excellent for diagnosing labral lesions. MRI is superior to CT in the imaging of all joint structures. Surgical approach can be accurately predicted with both imaging methods but special surgical techniques cannot be effectively planned to replace diagnostic arthroscopy in all cases.

Adult↗

Effects of estrogen or testosterone on self-reported sexual responses and behaviors in hypogonadal adolescents.

The purpose of this study was to investigate the effects of administration of sex steroids on self-reported sexual responses and behaviors in hypogonadal adolescents. We used a randomized, double blind, placebo-controlled, cross-over, clinical trial as the experimental design. The subjects were 39 boys and 16 girls with delayed puberty. We treated girls with oral conjugated estrogen and boys with testosterone enanthate in 3 dose levels intended to simulate early, middle, and late pubertal levels. We administered a modification of the Udry sexual behavior questionnaire after each 3-month placebo and treatment period to detect the effect of sex steroids on self-reported sexual behaviors and responses. We employed a strict intent to treat statistical analytical model. The data showed significant effects of the administration of testosterone to boys causing increases in nocturnal emission and touching behaviors at the mid- and high doses. No other treatment effects on sexual behaviors or responses were seen in boys. For girls, there was a significant increase in necking caused by the administration of estrogen only at the late pubertal dose. No other treatment effects on sexual behaviors or responses were seen in girls. We noted some gender differences for thinking about sex, sexual "turn-on," and the nature of sexual behavior. The administration of physiological doses of sex steroids to boys or girls with delayed puberty have few effects on sexual behaviors and responses.

Adolescent↗

Estrogen or testosterone increases self-reported aggressive behaviors in hypogonadal adolescents.

A randomized, double-blinded, placebo-controlled cross-over clinical trial was used to determine the role of sex steroids on the development of aggressive behaviors in 35 boys and 14 girls. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks alternating with placebo at three dose levels approximating early, middle and late pubertal amounts. The Olweus Multifaceted Aggression Inventory was administered after each placebo and treatment period to ascertain the effect of sex steroids on self-reported aggressive behaviors. We employed a strict intent-to-treat analytical model. The data demonstrated significant hormone effects on physical aggressive behaviors and aggressive impulses, but not in verbal aggressive behaviors nor aggressive inhibitions in both boys and girls. These results are the first to causally relate the administration of physiological doses of sex steroids to changes in aggressive behaviors in adolescents.

Adolescent↗

Use of cytomegalovirus immunoglobulin in multiply transfused premature neonates.

We undertook a randomized, placebo-controlled, double blind trial of cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or placebo was given within 24 hours of the first transfusion and at Day 10. If an intravenous catheter was still in place an additional dose was given between Days 20 and 30. The globulin and placebo groups were well-matched with respect to birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother, requirement for assisted ventilation and exposure to CMV-positive, unscreened blood products. Among infants followed for more than 10 days, 18 (10.5%) developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG). Among infants born to a CMV-seropositive mother, CMVIG use was associated with a CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to 12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P = 0.163). Among placebo recipients infants born to CMV-seropositive mothers were more likely to have a virologically confirmed CMV syndrome than those born to a CMV-seronegative mother, despite receipt of blood not screened for CMV antibody (P = 0.012). Multivariate analysis demonstrated that two factors were independently associated with CMV acquisition: the volume of CMV-seropositive blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that perinatally acquired CMV disease is more common among infants born to CMV-seropositive mothers than CMV-seronegative mothers, even without use of CMV-screened blood products.

Antibodies, Viral↗

Imaging rheumatoid arthritis joints with technetium-99m labelled specific anti-CD4- and non-specific monoclonal antibodies.

A direct comparison of the joint-imaging properties of inflammation-specific- and non-specific monoclonal antibodies (Mabs) was possible in a patient suffering from long-standing, severe rheumatoid arthritis (RA). This patient received an anti-CD4- and an anticarcinoembryonic antigen (anti-CEA) Mab, both labelled with technetium-99m, 9 days apart from each other. The anti-CD4 Mab was superior to the isotype-matched anti-CEA Mab in imaging inflamed joints. In the knee joint, the target-to-background ratio of the synovial membrane (SM) activity in comparison to that of adjacent large vessels was 1.22 (SM/muscle 1.55) for the anti-CD4 Mab and 0.53 (SM/muscle 0.92) for the anti-CEA Mab, in both cases 4 h after injection of the immunoglobulin. Since the CD4 antigen is present on the surface of T-helper lymphocytes and macrophages infiltrating the inflamed synovial membrane, imaging with the anti-CD4 Mab may allow more specific detection of inflammatory infiltrates in RA.

Aged↗

Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT.

Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P = 0.002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences.

AIDS-Related Opportunistic Infections↗

Precursor frequencies for DNA-specific B lymphocytes in patients with systemic lupus erythematosus (SLE).

Precursor frequencies for anti-DNA-secreting B cells were estimated in six healthy donors and 18 SLE patients with active and inactive disease. Precursors for IgG anti-dsDNA-secreting B cells were exclusively detected in SLE patients (73% of active patients and one inactive patient, 0.01-0.99% of IgG-producing B cells). These frequencies were in the same order of magnitude as frequencies of precursors for IgG anti-tetanus toxoid, which were detectable in three healthy volunteers after booster vaccination (0.07-0.8% of IgG-producing B cells), but not before (< 0.01%). Precursors for IgG anti-ss-DNA secreting B cells were observed in 33% of healthy donors and in 78% of SLE patients (0.01-0.32% of IgG-producing B cells). Only patient-derived IgG anti-DNA clones cross-reacted with (33%) or were monoreactive to dsDNA (12%). Precursors for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactivities with ssDNA and dsDNA. Segregation analyses and sorting experiments showed that > 94% of clones secreting IgG anti-DNA were derived from in vivo sIgG+ B cells. sIgM+ B cells were induced to switch in vitro; however, only twice were cultures containing IgM and IgG anti-DNA antibodies observed under clonal conditions. In conclusion, our results indicate that precursor B cells for IgG anti-dsDNA in SLE patients are similarly selected and expanded as are precursor B cells specific for foreign antigens such as tetanus toxoid.

Adult↗

RS3PE syndrome: no evidence for retroviruses.

OBJECTIVE: To determine whether human T cell lymphotrophic virus (HTLV) infection is associated with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. METHODS: Three patients presenting with RS3PE syndrome and 7 controls were examined for the presence of HTLV crossreactive antigens. RESULTS: Our patients were elderly men who presented with typical symptoms of abrupt onset of synovitis of the wrist, carpal joints, metacarpophalangeal, proximal interphalangeal, distal interphalangeal joints, and flexor tendons, associated with remarkable pitting edema of the hands. Transmission electron microscopy and immunohistochemical analysis for HTLV-1 P19 and P20 related antigens failed to detect retroviral presence in the sample specimens or controls. CONCLUSION: Our investigation suggests there is no evidence for HTLV synovial infection associated with RS3PE.

Aged↗

Immune restoration in children after partial splenectomy.

Splenectomy (SE) is recognized to be a therapeutical approach in treating children with severe autoimmune diseases (chronic idiopathic thrombocytopenia; hemolytic anemia) or hypersplenism because of portal hypertension. Nevertheless, removal of a main immune organ results in elevated infection risk for these patients. Partial splenectomy (PSE) was developed as a therapeutical compromise to retain immunologically active spleen tissue. Here, we document the analysis of immune parameters obtained from children after both partial and total splenectomy, which have been followed up for a period of more than 6 years: (i) Lymphocytes from both groups of patients failed to produce IgG in response to pokeweed mitogen in vitro. This was observed in 11/20 splenectomized patients even 10 years after operation, whereas in PSE patients a restoration of this parameter after 1-2 years was seen. (ii) In patients after PSE, but not in splenectomized persons, an elevated number of HLA-class II positive cells had been detected suggesting a different situation of immune regulation following this operation. However, in parallel with an improvement of B cell in vitro activity this parameter was found to achieve normal values. Our findings indicate that partial splenectomy may be a therapeutical alternative, if the therapeutic goal can be achieved by this procedure.

Adolescent↗

Comparison of 99Tcm-labelled specific murine anti-CD4 monoclonal antibodies and nonspecific human immunoglobulin for imaging inflamed joints in rheumatoid arthritis.

Inflamed joints in human rheumatoid arthritis (RA) can be imaged employing 99Tcm-labelled anti-CD4 monoclonal antibodies (MAbs). These MAbs recognize the CD4 molecule expressed on T-helper cells and, with a lower density, on macrophages, which are both abundantly present in RA inflammatory infiltrates. However, it is at present unclear whether specific binding to target molecules in the inflamed joint determines the joint uptake of anti-CD4 MAbs, i.e. whether the uptake of anti-CD4 MAbs differs from that of control immunoglobulins with irrelevant specificity. Eight patients with severe, active RA were examined after intravenous injection of a 99Tcm-labelled murine anti-human CD4 MAb (MAX.16H5; 200-300 micrograms, 370-550 MBq) or polyclonal human immunoglobulin (HIG; Technescan, MDH-67, Mallinckrodt Diagnostica; 1 mg, 370 MBq); five patients received both the anti-CD4 MAb and HIG. Whole body and joint scans in anterior and posterior views were obtained 1, 4 and 24 h after injection. As early as 4 h after injection, the anti-human CD4 MAb showed a higher target-to-background ratio in arthritic knee and elbow joints in comparison to polyclonal HIG used for conventional imaging, indicating that that anti-CD4 MAb allows more specific detection of inflammatory infiltrates rich in CD4-positive cells.

Adult↗

[High-dose immunoglobulin therapy of rheumatoid arthritis].

Eight patients suffering from severe rheumatoid arthritis were treated with high-dose human immunoglobulin. Doses of 500 mg/kg were administered intravenously in the morning on 4 consecutive days. Improvement of arthritic symptoms was indicated by a significant decrease of the Ritchie index, the number of swollen joints, and the duration of morning stiffness as well as an increase of grip strength. The improvement lasted up to 4 months. In 2 patients the disease activity increased again after 4 weeks. Investigations of laboratory parameters demonstrated a significant reduction of the acute-phase response. Parallel investigations of immunological parameters revealed a decrease of Il-6 levels in the sera. Therefore, we suggest a decreased activation status of the monocyte-macrophage system and T cells as a possible mode of action of high-dose immunoglobulin therapy in rheumatoid arthritis.

Aged↗

Lymphocyte surface marker expression on hybridomas secreting human monoclonal antibodies.

The expression of human leucocyte markers on the surface of hybridoma cell lines producing human monoclonal antibodies was studied using immunofluorescence analysis (FACS). We tested 36 different hybridoma cell lines from fusions of lymphocytes of different organs of fetal and adult organisms with the mouse myeloma line P3 X63 Ag8.653 or the mouse-human heteromyeloma line CB-F7 (IgM-, IgG-, and nonproducer) with a panel of 21 murine monoclonal antibodies against human differentiation and activation antigens. CD2, 3, 4, 5, 8, 10, 23, 25 antigen and major histocompatibility complex (MHC) class II determinants could not be detected on all hybridomas analyzed. The antigens CD22, 69, 71, and 72 were expressed on few of the hybridomas tested. The majority of the cell lines carried the surface markers CD19, 20, 40, 45 as well as the plasma cell markers CD38 and O/C11. The activation antigen 4F2 was expressed on all the cell lines tested. However, a direct connection between the expression of a lymphocyte marker and the capacity for Ig production (high and low producer; Ig isotype), the origin of the lymphocytes, and the fusion cell line used could not be detected.

Antibodies, Monoclonal↗