Publications

Chest compression is an important part of cardiopulmonary resuscitation (CPR), but it only aids circulation during a portion of the compression cycle and has been shown to only minimally increase blood flow to vital organs. The purpose of this study was to quantitate the short-term hemodynamic effects of CPR with a hand-held suction device that incorporates both active compression and decompression of the chest. The suction device was applied to the middle of the sternum and compared with standard manual CPR in eight nonventilated anesthetized dogs. Coronary perfusion pressure, systolic and diastolic aortic pressures, right atrial diastolic pressure, and the velocity time integral (an analog of cardiac output), which were obtained by means of transesophageal pulsed wave Doppler echocardiography from the main pulmonary artery, were measured every 30 seconds during CPR. Minute ventilation was measured over the last minute of each CPR technique. Both active compression-decompression CPR and standard CPR were sequentially performed for 2 minutes in random order 30 seconds after induced ventricular fibrillation. The CPR techniques consisted of 100 compressions per minute, with a compression depth of 1.5 to 2 inches and a 50% duty cycle. Coronary perfusion pressure, velocity time integral (cardiac output analog), minute ventilation, and systolic arterial pressure were all significantly improved by active compression-decompression CPR when compared with standard CPR. We conclude that active compression-decompression CPR is a simple technique that appears to improve coronary perfusion pressure, systolic arterial pressure, cardiac output, and minute ventilation in nonventilated animals when compared with standard CPR.(ABSTRACT TRUNCATED AT 250 WORDS)

IL-2 is one of the principal growth factors regulating the proliferation of T lymphocytes. Although two independent IL-2-binding molecules have been molecularly cloned and shown to participate in the formation of a high affinity receptor complex, their primary structures do not suggest a specific mechanism for IL-2 growth signal transduction across the cell membrane. Neither IL-2 receptor subunit contains an intrinsic kinase domain; nevertheless, tyrosine phosphorylation of various intracellular substrates is one of the first biochemical changes observed following activation of the IL-2 receptor (IL-2R). Both serine/threonine and tyrosine kinases can be co-precipitated as part of the IL-2R complex suggesting that the IL-2 signalling may involve the activation of non-covalently associated intracellular kinases. However, controversy exists as to which kinases are involved in IL-2 signal transduction; in particular, which kinase(s) mediates the first or proximal event(s) in the signalling process. Activation of the IL-2R leads to serine and threonine phosphorylation of the SRC tyrosine kinase family member, LCK, and an increase in LCK tyrosine kinase activity. Furthermore, LCK can be co-immunoprecipitated with the beta chain of the IL-2R indicating its association with the receptor complex. IL-2 has also been reported to increase FYN kinase activity and to alter its association with the 85 kDa subunit of phosphatidylinositol-3 kinase thus suggesting a role for FYN in IL-2 signal transduction. However, in this report, we now demonstrate that neither LCK nor FYN are obligatory for IL-2-induced growth of HTLV-I-infected human T cells. Lack of expression of LCK or FYN in the HTLV-I-infected T cell lines was demonstrated by a combination of Northern blotting, polymerase chain reaction, Western blotting, and in vitro kinase activity. Despite the absence of LCK or FYN, IL-2 induced similar patterns of rapid tyrosine phosphorylation. Similar results were observed in cell lines lacking expression of the LYN, FGR, HCK, and LTK tyrosine kinases. Thus, none of these tyrosine kinases alone appears to be required for growth signalling through the IL-2R in the HTLV-I-infected T cell lines analyzed. The findings raise the possibility that an, as yet, unidentified tyrosine kinase is involved. Alternatively, this biological signalling system may exhibit remarkable redundancy whereby several different tyrosine kinases may be capable of associating with the IL-2R complex and mediating intracellular signalling.

Chronic administration of anti-CD4 mAb prevents autoimmune disease in NZB/NZW F1 (B/W) mice. This may be due either to CD4 cell depletion or to inhibition of CD4 cell function. To evaluate the relative importance of these mechanisms, we devised a system in which the consequences of cell depletion could be analyzed independent of the inhibitory effects of chronic mAb therapy. This was accomplished by performing adult thymectomy before mAb administration. Specifically, female B/W mice underwent thymectomy or sham thymectomy at age 6 wk, followed at age 3 mo by a short course of either anti-CD4 (2 mg/wk for 3 wk) or saline. Treatment with anti-CD4 depleted 90% of circulating CD4 cells, but a small subpopulation (10%) of CD4 cells was refractory to depletion. In non-thymectomized mice, the CD4 population gradually reconstituted after cessation of therapy. In contrast, in thymectomized mice, recovery of CD4 cells was prevented by the absence of the thymus. Despite the striking reduction in CD4 cells in thymectomized mice, severe autoimmune disease developed, with autoantibody levels, proteinuria, and mortality comparable with non-thymectomized, nondepleted controls. The unexpected development of lupus nephritis in thymectomized, CD4-depleted B/W mice suggested that the thymus might be required to achieve the benefits of therapy with anti-CD4. To exclude this possibility, we demonstrated that chronic therapy with anti-CD4 prevents autoimmunity in thymectomized B/W mice. These findings imply that: 1) substantial depletion of CD4 T cells is not sufficient to suppress autoimmunity; 2) suppression of autoimmunity requires sustained functional inhibition of CD4 T cells; and 3) a small subpopulation of CD4 cells that is refractory to depletion by anti-CD4 is sufficient to promote the full expression of murine lupus in B/W mice.

OBJECTIVES

The aims of this study were to better characterize valve disease in systemic lupus erythematosus and to determine its association with antiphospholipid antibodies.

BACKGROUND

Estimates of the prevalence of valve disease in systemic lupus erythematosus have been higher in autopsy series than in clinical studies using transthoracic echocardiography. Antiphospholipid antibodies have been suggested to be a primary pathogenetic factor.

METHODS

Transesophageal echocardiography was performed on 1) 54 patients with lupus erythematosus, 22 of them with (group I) and 32 without (group II) antiphospholipid antibody; 2) on 10 patients with antiphospholipid syndrome (group III); and 3) on 35 normal subjects (group IV).

RESULTS

Patients in groups I and III had similar types and concentrations of antibodies. Leaflet thickening was found in 50% of group I, 47% of group II, 10% of group III and 9% of group IV patients (group I or II vs. group III or IV, p < 0.03). Leaflet thickening in patients with lupus erythematosus was diffuse; it usually involved the mitral and aortic valves and was associated with valve regurgitation (73%) or valve masses (50%). Valve masses were observed in 41% of group I, 25% of group II, 10% of group III and in none of group IV patients (group I or II vs. group IV, p < 0.002). Most valve masses in patients with lupus erythematosus were located near the base on the atrial side of the mitral valve or on the vessel side of the aortic valve, had variable size (0.2 to 0.85 cm2), shape and echodensity. Valve regurgitation was observed in 64% of group I, 59% of group II, 10% of group III and 20% of group IV patients (group I or II vs. group III or IV, p < 0.006). Moderate or severe regurgitant lesions were noted in 27% of group I and 25% of group II patients.

CONCLUSIONS

Lupus erythematosus valve disease is frequent (74%) regardless of the presence or absence of antiphospholipid antibodies. Therefore antiphospholipid antibodies may not be a primary pathogenetic factor. The characteristic appearance of leaflet thickening and masses in patients with lupus erythematosus may be unique.