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T cell receptor-defined subsets of gammadelta T cells differentially localize in cutaneous, intestinal, or reproductive epithelium. In this issue of Immunity, Xiong et al. show that murine Vgamma3+ T cells undergo TCR-dependent selection in the fetal thymus that drives expression of a cutaneous homing receptor.
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OBJECTIVE: The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? METHODS: We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. RESULTS: The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. CONCLUSION: The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.
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Intraerythrocytic Plasmodium falciparum exports proteins to the cytosol and to the plasma membrane of the host cell. We here present data revealing the existence of a unique common pathway for the surface bound traffic of the clonally variant antigens, repeated-interspersed-antigen (RIFINS) and P. falciparum erythrocyte-membrane-protein-1 (PfEMP1). RIFIN- and PfEMP1-specific antibodies were found to stain single small vesicles (SSV) that bud off from the parasitophorus vacuolar membrane (PMV) at 6-10 h post-invasion. Large multimeric vesicle (LMV) assemblies, composed of subunits each of a similar size to that of a SSV, appeared as the dominant vesicle type carrying the variant antigens in the cytosol as the parasites developed into early trophozoite stages (> or = 16 h post-invasion). Later, more than 24 h post-invasion, large spinle-like vesicles (LSLV) built up as the LMV approached and accumulated underneath the erythrocyte membrane. LMV were found to associate both with the Maurer's cleft antigen Pf332 and with lipids as seen by fluorescent BODIPY-Ceramide staining. Co-traffic of Pf332 with RIFINS and PfEMP1 occurred in sub-compartmentalized LMV, as the variant antigens co-localized at the outer rim while Pf332 occupied the core of the vesicle complex. Formation of LMV for the trafficking of RIFINS and PfEMP1 is a prominent feature of freshly isolated P. falciparum and of in vitro propagated K+ as well as K- parasites, seemingly independent of the knob-associated histidine-rich protein (KAHRP). In vitro cultured 3D7 clones lack LMV formation and traffic the variant antigens in vesicles of a similar size to that of the SSV.
Transcriptional silencing in budding yeast and fruit fly is mediated by fundamentally unrelated proteins that assemble very different chromatin structures. Surprisingly, the repressive mechanisms evolved from these very different materials have similar features, including an epigenetic mode of inheritance and a block to transcription based on interference with the assembly or function of the promoter complex rather than with the binding of gene-specific activators.
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BACKGROUND: To evaluate the feasibility and efficacy of outpatient left ventricular assist devices as a bridge to transplantation, we reviewed the initial clinical experience with this modality at our institution. METHODS: During January 1993 to November 1995, 12 male and 2 female patients with an average age of 47 +/- 17 years were supported for an average of 117 +/- 24 days with the Thermo Cardiosystems VE wearable left ventricular assist device. Seven patients were discharged home an average of 35 +/- 4 days after implantation. RESULTS: No device failures occurred, although 29 controller malfunctions were identified during 1,640 total support days. All patients were able to safely maintain their devices. Outflow graft bleeding and driveline infection were responsible for two readmissions. No long-term anticoagulation treatment was used; one small thromboembolic episode occurred, but without significant long-term sequelae. CONCLUSIONS: None of the 7 patients released from the hospital died, and all were able to successfully maintain their devices at home. Hospital discharge of patients supported with left ventricular assist devices has allowed long-term evaluation of this technology, and the findings should prompt study of their use as a long-term alternative treatment to medical management for congestive heart failure.
OBJECTIVE: A mathematical model using selected items from the Functional Independence Measure (FIM) was developed to predict disposition of stroke patients from an acute care hospital. DESIGN: Case series of 279 acute stroke patients admitted to the hospital from 4/91 through 12/93. Data collection remains ongoing; a second series of patients will be analyzed to validate results and determine if the same 6 FIM items are significant. SETTING: Tertiary care center, general acute care community hospital. PATIENTS: Diagnosis of acute stroke; 298 patients whose attending physician referred the patient to the rehabilitation team. An 18-item FIM was administered within 3 days of admission and 24 hours of discharge. MAIN OUTCOME MEASURE: FIM scores were analyzed to determine if the initial score could be used to predict disposition. Discriminant analysis identified 6 items as being statistically significant in predicting discharge to home, rehabilitation facility, or nursing home. Patient's actual discharge location was compared with the location predicted by the model developed using the FIM. RESULTS: Bathing, bowel, toileting, social interaction, dressing lower body, and eating were the selected initial FIM items that predicted disposition with 70% accuracy in our patient series. CONCLUSION: The FIM is effective in the acute care setting to help determine appropriate discharge status, with certain variables being more predictive than others.
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OBJECTIVE: To assess the predictive value of E2, hCG, CA-125, and morphometric parameters in early pregnancies with demonstrable fetal heartbeat, complicated by bleeding. DESIGN: Prospective longitudinal follow-up. SETTING: The emergency service of the Department of Obstetrics and Gynecology, "Rebecca Sieff" Hospital, Safed, Israel. PATIENTS: Twenty-five consecutive patients with vaginal bleeding during weeks 7 to 12 of pregnancy who had demonstrable fetal heartbeat. Ten women with normal pregnancies, serving as controls. MAIN OUTCOME MEASURE: The serum levels and the morphometric parameters were related to the outcome of pregnancy as revealed by future hospitalization, delivery, or telephone questioning. RESULTS: In the five patients who eventually aborted, the values of CA-125 were > 125 U/mL, whereas none of the successful pregnancies had a value > 93 U/mL. The mean values were 133 +/- 4.85 versus 36.95 +/- 23.1 U/mL for miscarriages and successful pregnancies, respectively. In normal pregnancies the respective value was 32.3 +/- 4.3 U/mL. Although mean E2 levels were lower in the serum of women who eventually aborted, there was a significant overlap of values with the successful pregnancies. All the other parameters measured had no correlation to the outcome of these pregnancies. CONCLUSION: CA-125 may serve as an accurate predictor of the outcome in early pregnancies with demonstrable fetal heartbeat, which are complicated by bleeding.
OBJECTIVE: To compare salivary cortisol levels and maternal anxiety (general and pregnancy-specific) in the early and late second trimester of pregnancy between women who developed preeclampsia (PE) and women who remained normotensive. DESIGN: Nested case-referent study. In a prospectively studied cohort of 250 pregnant women, nine women developed PE in late pregnancy. These nine patients were matched and compared with nine controls. Diurnal cortisol levels were obtained by collecting saliva samples at 17-18 and 27-28 weeks gestation. Salivary cortisol levels were determined by radioimmunoassay. Maternal anxiety was determined by Spielberger's State-Trait Anxiety Inventory (STAI) and a pregnancy-specific stress questionnaire. RESULTS: For both patients and controls, a similar pattern of salivary cortisol excretion was observed. Salivary cortisol levels and anxiety scores (general and pregnancy-specific) did not differ significantly between patients and controls. CONCLUSIONS: Our findings do not lend support to a role for maternal anxiety or second trimester increases in circulating stress hormones in the pathogenesis of PE.
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