Comparison of pulse contour analysis by Pulsioflex and Vigileo to measure and track changes of cardiac output in critically ill patients.

BACKGROUND: We compared the new Pulsioflex and the Vigileo devices to measure cardiac index (CI) in critically ill patients. Both devices measure CI by pulse-contour analysis. The Pulsioflex device also allows an auto-calibration (not based on thermodilution). METHODS: Patients were included if we administered fluids (20 patients), reduced (20 patients), or increased (20 patients) the dose of norepinephrine. Before and after interventions, we measured CI provided by the Vigileo (CIVig) and Pulsioflex (CIPfx) devices before and after its auto-calibration. CI measured by transpulmonary thermodilution (CIthermo) was used as the reference. RESULTS: Considering absolute values of CI (n=120), the percentage error was 59% for CIVig vs CIthermo and 40% for CIthermo vs CIPfx. Auto-calibrating CIPfx after interventions did not improve the percentage error between CIPfx and CIthermo (39%). Considering the fluid-induced changes in CI, the coefficient of correlation with changes in CIthermo was 0.50 for CIVig, and 0.73 for CIPfx (P=0.27). It was not significantly improved if CIPfx was auto-calibrated (r=0.64). Considering the norepinephrine-induced changes in CI, the coefficient of correlation with changes in CIthermo was 0.41 for CIVig. It tended to be better for CIPfx (r=0.71, P=0.07). It was not significantly improved by auto-calibration (r=0.53). CONCLUSIONS: The Pulsioflex did not reliably estimate the absolute values of CI. For tracking fluid-induced changes in CI, the Pulsioflex was reliable, and also the Vigileo. For tracking norepinephrine-induced changes in CI, it was also reliable and tended to be better than the Vigileo. Auto-calibration allowed by the system did not improve its reliability.

Impaired activity of natural killer cells in patients with acute brucellosis.

Researchers have claimed that natural killer (NK) cells are involved in the mechanisms of defense of the host against infections. We have investigated the activity of NK cells in peripheral blood mononuclear cells (PBMNC) from 12 patients for whom acute brucellar infection has been diagnosed and from 14 healthy controls. The sera of eight of the patients were also analyzed 3 months after initiation of a 45-day course of antibiotic treatment, at which time they had no evidence of relapse. PBMNC from patients with acute brucellar infection showed a significantly depressed NK cell activity (P < .01) when compared with those from healthy controls; this depressed activity was not related to a deficient number of NK cells since the numbers of CD56+ and CD16+ cells present in PBMNC were similar in patients and controls. Incubation of PBMNC from patients with acute brucellar infection with recombinant interleukin-2, but not with interferon-gamma, can correct this impaired cytotoxic activity. In treated patients, there was a significant enhancement (P < .05) and normalization of the previously defective NK cell activity. It is concluded that acute brucellar infection is associated with a deficient cytotoxic activity of NK cells that can be overcome by in vitro incubation with interleukin-2 and that reverts to normal after antibiotic treatment.

Two different maturational stages of natural killer lymphocytes in human newborn infants.

The objective of this study was to assess the basis for the diminished natural killer (NK) lymphocyte activity of neonates. We found either severely reduced (63% of 68 neonates) or normal (similar to healthy adult) levels of NK activity. The percentages of cord blood mononuclear cells from the two groups of infants that expressed CD16, a differentiation antigen found in NK cells, were similar and within the range found in peripheral blood mononuclear cells of adults. However, infants with low NK activity had reduced numbers of cells in the CD16+56+ subpopulation, whereas the number of these effector cells present in cord blood mononuclear cells from infants with normal NK activity was within the range found in adults. Recombinant interleukin-2, but not recombinant interferon-gamma, normalized the low NK activity of infants in a dose- and time-dependent manner. Analysis of the pattern of target cell susceptibility to lysis, together with the CD16+CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. In contrast, NK cells from infants with normal cytotoxic levels exhibited a functional response to interleukin-2 and interferon-gamma similar to that of adults. Our results indicate that NK cells in human neonates go through two different maturational stages.

Diminished natural killer activity in pregnancy: modulation by interleukin 2 and interferon gamma.

We investigated the alterations of natural killer (NK) cells in pregnancy, which led to decreased killing from the first trimester to the puerperium. We show that this phenomenon cannot be ascribed to a defective number of NK cells since the amounts of HNK-1+, CD16+ (Leu 11), and CD11b+ (OKM1) cells were within normal ranges. Recombinant interleukin 2 (rIL-2) corrects the functional defect in a dose and time-dependent manner, without modification in the surface phenotype of the population. Analysis of the pattern of target cell susceptibility to lysis, together with the similar ability of recombinant interferon gamma (rIFN-gamma) to correct the deficiency, and CD16+, CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. Inhibitors in pregnancy sera block IL-2 production by specific T cells, but we show that they do not influence either NK activity or its reconstitution by rIL-2. These findings place the deficiency at the level of NK cell maturation into cytotoxic effector lymphocytes. Thus, homeostasis of the NK activity of pregnant women may provide a biological model for clarifying the internal mechanisms regulating NK-cell activation in vivo. Present studies in vitro suggest that modulation of lymphokine production may play a role in the adaptive response of NK cells in pregnancy.

[Immunobiology of materno-fetal relations]. / Inmunobiología de las relaciones materno-fetales.

Normal development of pregnancy requires maternal immune system tolerance towards the fetoplacental allograft. Natural Killer (NK) cells can display spontaneous lytic activity against tumoral, and poorly differentiated cells, without a prior sensitization. Moreover this cytotoxic activity is not restricted by the Major Histocompatibility Complex (MHC). We investigated the existence of modifications in the NK activity mediated by peripheral blood mononuclear cells (PBMC) from pregnant women. A significant depression was found in this activity from the first trimester to the puerperium that cannot be ascribed to a defective number of NK cells among pregnant's PBMC. However this impaired NK activity can be reconstituted in vitro by incubation of PBMC with interleukin 2 (IL 2). Pregnancy is also associated with an absence of effectors and/or precursors which mediate other cytotoxic non MHC-restricted activities after long term incubation with IL 2, the so called Lymphokine Activated Killer (LAK) cells.

Clinical implications of natural killer (NK) cytotoxicity in patients with squamous cell carcinoma of the uterine cervix.

Natural killer (NK) activity in peripheral blood mononuclear cells (PBMC) from women with squamous cell carcinoma of the uterine cervix (SCCUC) was studied. PBMC were obtained from 26 previously untreated patients with SCCUC at different stages of disease according to the FIGO classification (5 at stage I, 4 at stage II, 5 at stage III, 6 at stage IVa, and 6 belonging to stage IVb), as well as from 23 healthy age-matched women. These cells were used as effectors against 51Cr-labeled K-562 target cells in standard 4-hr cytotoxic assays. The NK activity displayed by PBMC from patients with local stages of the neoplasm (I, II, III, and IVa) was found to be similar to that exerted by PBMC from healthy controls (P greater than 0.05). Furthermore, there were no significant differences among mean values of NK activity in PBMC from women at these different stages of the disease (P greater than 0.05). However, the NK activity detected in the PBMC of patients with distant metastatic spread of the disease (stage IVb) was significantly depressed with respect to both controls and patients at any other earlier stage (P less than 0.05). We conclude that a decrease in the NK activity present in PBMC from women with SCCUC coincides with distant tumoral dissemination of the disease.

Pregnancy is associated with a reduction in the pattern of the cytotoxic activity displayed by lymphokine-activated killer cells.

Several modifications in the homeostasis of the maternal immune system have been implicated in the survival of the fetoplacental graft. We have investigated the adaptive response of the cytotoxic nonmajor histocompatibility complex (MHC)-restricted effector lymphocytes in pregnancy, and have found that the spontaneous lytic activity against both natural killer (NK)-sensitive and NK-resistant target cells is either decreased or lacking in peripheral blood mononuclear cells (PBMNC) from pregnant women. Recombinant interleukin-2 (rIL-2) normalizes the cytotoxic activity of PBMNC from pregnant women against NK-sensitive target cells in a dose- and time-dependent manner, without modification in the normal amounts of HNK-1+, CD16+ (Leu 11, or CD11b+ (OKM-1) present in these effector populations. However, the pattern of lytic activity against NK-resistant target cells found in PBMNC from pregnant women after short- and long-term incubation with rIL-2 was reduced in comparison with that observed in PBMNC from nongravid women in similar conditions. Moreover, rIL-2 incubation of PBMNC from pregnant subjects was not associated with an enhancement of the lytic binding against NK-resistant target cells. These findings demonstrate that pregnancy is not only associated with a reduction in the NK lytic activity of PBMNC, but also with a reduction in the generation of lymphokine-activated killer activity, in terms of the pattern of lytic activity developed.