Thrombolysis in acute stroke without angiographically documented occlusion.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) using urokinase (UK) in acute stroke patients without angiographically-documented occlusion, and to define predictors of clinical outcome. PATIENTS AND METHODS: We analyzed clinical and radiological data of acute ischemic stroke patients whose angiography did not show an arterial occlusion within six hours of symptom onset and who were further treated with IAT using UK. The primary outcome was a modified Rankin Scale (mRS) score ≤ 2 at 90 days' post procedure. RESULTS: In a thrombolysis database of 263 patients, we identified 51 patients without angiographically-documented arterial occlusion who received IAT with UK within six hours of symptom onset. The median baseline NIH stroke scale measurement was 11 (range: 8-20). From symptom onset, the mean time to treatment was 4.1 ± 1.3 h (median: 4.5 h; range: 1.5-6.0 h). Immediate and dramatically clinical improvement was seen in 29/51 (56.9%) patients. One patient (2.0%) developed a symptomatic intracranial hemorrhage. At three months, 38/51 (74.5%) patients were independent (mRS ≤2), 13/51 (25.5%) patients were dependent (mRS > 3), and no patients died. No predictors of clinical outcome were identified. CONCLUSIONS: IAT using UK can be a safe and efficacious therapy for the treatment of acute ischemic stroke in patients without angiographic occlusion. Approximately 75% of these patients had a favorable clinical outcome and thrombolysis-related symptomatic hemorrhage was low.

Specific antibody responses to synthetic peptides of HIV-1 p17 correlate with different stages of HIV-1 infection.

Antibodies were determined against five synthetic peptides (epitopes) of HIV-1 p17 in the sera of an immunologically and clinically well-characterized cohort (N = 292) of HIV-1 seronegative and HIV-1 seropositive high-risk homosexual men, HIV-1 seropositive i.v. drug abusers (IVDA), and AIDS patients. The synthetic peptides, representing the entire HIV-1 p17 protein sequence were: HGP-33 (aa 1-33), HGP-19 (aa 34-52), HGP-35 (aa 51-85), HGP-30 (aa 85-114), and HGP-17 ala (aa 114-131). The presence of one or more peptide-specific antibodies in the sera of all of the HIV-1 p17-positive subjects indicated that all five peptides contain B-cell epitopes. No antibodies were found in the sera of heterosexual controls, HIV-1 seronegative high-risk men, or asymptomatic HIV-1 seropositive but p17 antibody-negative study subjects. Significant differences in antibody recognition profiles to the peptide epitopes were found among the various study groups. A significantly higher proportion of HIV-1 seropositive IVDA had antibodies specific to HGP-17 ala (aa 114-131), HGP-35 (aa 51-85), and HGP-33 (aa 1-33) compared to the HIV-1 p17-positive asymptomatic homosexuals. The epitope-specific antibody responses reflected the clinical status of the HIV-1-infected study subjects, and declined to nondetectable levels as the patient progressed to ARC/AIDS. This decline preceded by several months the reduction in the antibody titer against the intact HIV-1 p17 and p24 proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Inverse relationship between HIV-1 p24 antigenemia, anti-p24 antibody and neutralizing antibody response in all stages of HIV-1 infection.

A double blind cohort study was conducted on 149 homosexual males and 36 patients with AIDS to investigate the relationship between HIV-1 antigenemia, the presence of neutralizing antibody (NA) activity and specific anti-viral core protein (p24) antibody (Ab) in the sera of HIV infected individuals during their progression to AIDS. All AIDS patients and 68% (101/149) of the homosexual males were HIV seropositive upon entering the study. Of those 48 (32%) homosexuals who were HIV negative at the onset, three seroconverted during the two year observation period. Retrospective studies of the HIV(-) subjects' sequentially stored serum samples demonstrated an early transient appearance of gag encoded p24 antigen (Ag) which preceded their production of NA and specific anti-p24 Ab. Following their seroconversion, no more circulating p24 Ag could be detected. Among the 101 HIV positive homosexuals, 16% rapidly progressed to AIDS and seven of these 16 (44%) subjects eventually died during the two year observation period. In this group of individuals with poor prognosis, presence of NA and anti-p24 Ab commenced at the onset reaching peak levels just prior to developing AIDS and began to decline as the clinical course worsened. Their circulating level of p24 Ag remained undetectable as long as there was quantifiable NA and anti-p24 Ab in their sera. Reappearance of circulatory p24 Ag, on the other hand, was associated with high risk for progression to AIDS.2+hus, while only 11

Results of 110 vitrectomies with a portable vitrectomy system.

We retrospectively evaluated the VITAC (vitreous-tissue aspiration cutter), a portable vitrectomy system with an end-cutting vitrectomy probe with a self-sharpening oscillating blade and a monoblock design, in 110 vitrectomy procedures, 34 performed at the University of California Davis Medical Center and 76 performed at the Eye and ENT Hospital in Shanghai, China. The indications for vitrectomy included penetrating injuries (22 eyes), intraocular foreign bodies (28 eyes), vitreous hemorrhages (18 eyes), cataracts (17 eyes), endophthalmitis (seven eyes), pupillary-block glaucoma (five eyes), bullous keratopathy (five eyes), aphakic penetrating keratoplasty (three eyes), pupillary membranes (two eyes), massive preretinal proliferation (one eye), and cystoid macular edema (one eye). Vitrectomy resulted in visual improvement in 19 of 34 eyes in the California series (56%) and in 60 of the 76 eyes in the Shanghai series (79%). This difference was attributable to the higher percentages of cases involving the posterior segment and vitreous hemorrhage in the California series. When results from both institutions were combined, surgery with the VITAC produced visual improvement in 79 of 110 cases (72%), comparable to the results obtained with other vitrectomy systems.

Impairments in functional subsets of T-suppressor (CD8) lymphocytes, monocytes, and natural killer cells among asbestos-exposed workers.

Peripheral blood leukocytes from asbestos-exposed workers were analyzed by dual color flow cytometry using monoclonal antibodies that identify developmental (HLA-DR) and functional (Leu 8) subsets of T helper, suppressor lymphocytes, and monocytes. An increase in the number of T suppressor cells was closely associated with a decrease in T lymphocyte functions while numerical defects in activated monocytes (Leu M3+Ia+) and natural killer cells (Leu 7+) were correlated with a depressed Th/Ts ratio. Furthermore, among asbestos-exposed workers with depressed T cell functions we have demonstrated a significantly higher number of the effector Ts (Leu 2+ Leu 8-) subset which regulates both the Th/Ts lymphocyte system as well as B cells and NK cell activities. These findings identified changes in the T suppressor feedback regulatory loop as being responsible for the immunoregulatory imbalance among long-term asbestos workers. In double blind analyses of demographic and radiographic data these phenotypic changes were not correlated with age, smoking history, or duration of exposure but were associated with radiographic evidence of asbestos-associated effects. This correlation established a direct link between asbestos exposure and the subsequent development of immune dysfunction.

A distinctive form of soluble CD8 is secreted by stimulated CD8+ cells in HIV-1-infected and high-risk individuals.

The aim of the present study was to investigate the biochemical structure and pathogenic significance of the soluble CD8 (sCD8) present in the serum of HIV-1-infected individuals. In a longitudinal study of a cohort of HIV-infected homosexuals and the amount of sCD8 detected in the plasma was correlated with changes in lymphocyte subsets and with the clinical course of HIV infection. The level of sCD8 in the plasma, the percentage, and the absolute number of CD8+CD38+ cells were increased in HIV-seronegative, high-risk homosexuals and in seropositive HIV+ individuals. The plasma concentration of serum sCD8 showed a significant correlation with the absolute number of CD8+ and CD8+CD38+ cells in HIV+ homosexuals. In addition to a molecule with a molecular weight (m.w.) of 30 kDa, sCD8 isolated from the plasma of HIV-1-infected individuals and of healthy controls was found to consist of two molecules, one with a m.w. of 57 to 62 kDa and another with a m.w. of 66 to 70 kDa. The former was the predominant molecule in normal individuals, while the latter was the predominant molecule in HIV-negative high-risk homosexuals and in HIV-infected individuals. The latter molecule, secreted by chronically stimulated CD8+ cells, seems to be present in the circulation as a dimer. While it was previously shown that CD8 can be shed from the cell membrane in vitro, the present study indicates that in vivo-stimulated CD8+ cells release a distinctive form of soluble CD8.

Increases in soluble CD8 antigen in plasma, and CD8+ and CD8+CD38+ cells in human immunodeficiency virus type-1 infection.

Increases in plasma levels of soluble CD8 (SCD8) antigen and expansion of the CD8+ CD38+ lymphocyte compartment were early immunologic alterations frequently observed prior to detection of antibodies against human immunodeficiency virus type 1 (HIV-1) and diminution of CD4+ cells in subjects at risk to develop AIDS. These increases identified in the 49 seronegative homosexual men were manifest in all 164 homosexual subjects and 45 intravenous drug users (IVDU) positive for HIV-1 antibodies (HIV-1+), 19 patients with ARC, and 29 AIDS patients. Augmentation of plasma sCD8 antigen correlated with increases in both CD8+ and CD8+ CD38+ cells in HIV-1(-) homosexual men (r = 0.35, P less than 0.013; r = 0.48, P less than 0.0005; respectively) and the 258 HIV-1+ subjects (r = 0.25, P less than 0.0003; r = 0.33, P less than 0.0001, respectively). In vitro examination of unstimulated peripheral blood lymphocytes from HIV-1+ homosexuals and IVDU confirmed the fivefold higher constitutive levels of cellular release of sCD8 antigen in these subjects compared to heterosexual controls. Inclusion of radiolabeled amino acids during the 3-day culture period in the presence or absence of phytohemagglutinin resulted in negligible levels of radioactivity associated with the sCD8 antigen indicative of a lack of de novo synthesis. Throughout clinical progression to AIDS, sCD8 antigen levels continued to escalate relative to the numbers of CD8+ cells bearing CD38+ antigen. The data confirm the interrelationship between sCD8+ antigen and CD8+ and CD8+ CD38+ cells.