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Biomedical subjects

R Giuliani

Publications and source records attributed to R Giuliani.

At least 19 recordsLinked to original sources
PubMed1999

Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo.

Hematopoietic and endothelial cell lineages share common progenitors. Accordingly, cytokines formerly thought to be specific for the hematopoietic system have been shown to affect several functions in endothelial cells, including angiogenesis. In this study, we investigated the angiogenic potential of erythropoietin (Epo), the main hormone regulating proliferation, differentiation, and survival of erythroid cells. Epo receptors (EpoRs) have been identified in the human EA.hy926 endothelial cell line by Western blot analysis. Also, recombinant human Epo (rHuEpo) stimulates Janus Kinase-2 (JAK-2) phosphorylation, cell proliferation, and matrix metalloproteinase-2 (MMP-2) production in EA.hy926 cells and significantly enhances their differentiation into vascular structures when seeded on Matrigel. In vivo, rHuEpo induces a potent angiogenic response in the chick embryo chorioallantoic membrane (CAM). Accordingly, endothelial cells of the CAM vasculature express EpoRs, as shown by immunostaining with an anti-EpoR antibody. The angiogenic response of CAM blood vessels to rHuEpo was comparable to that elicited by the prototypic angiogenic cytokine basic fibroblast growth factor (FGF2), it occurred in the absence of a significant mononuclear cell infiltrate, and it was not mimicked by endothelin-1 (ET-1) treatment. Taken together, these data demonstrate the ability of Epo to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo and thus act as a bona fide direct angiogenic factor.

Allantois↗
PubMed1999

Time-course of impairment of respiratory mechanics after cardiac surgery and cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with abnormalities of lung function characterized by an increase in static elastance of the respiratory system. We examined the following: a) the effects of CPB on the total inspiratory volume-pressure (V-P) relationship of the respiratory system; b) the relative contribution of the chest wall and lung to the impairment of respiratory system mechanics; and c) the time-course of such impairment. DESIGN: Prospective, interventional study. SETTING: Surgical and medical intensive care units in a teaching hospital. PATIENTS: Eight adult patients scheduled for elective open heart surgery to correct valvular dysfunction. INTERVENTIONS: V-P curves (interrupter technique) of the respiratory system were partitioned between the chest wall and lung by measurements of esophageal pressure. Measurements were obtained before sternotomy (control), immediately after, 4 hrs after, and 7 hrs after separation from CPB. MEASUREMENTS AND MAIN RESULTS: Control V-P relationships of the respiratory system and lung showed lower inflection points (Pflex) at pressure values of 5.9+/-2.3 and 4.3+/-2.5 cm H2O, respectively. Immediately after and 4 hrs after separation from CPB, both curves had sigmoid shapes because of lower Pflex and formation of upper inflection (UIP) points. The pressures corresponding to the Pflex increased significantly (p < .001) by 56%+/-3% and 78%+/-4%, whereas the UIP corresponded to a pressure value of 42.34+/-8.5 and 35.6+/-7.8 cm H2O in the respiratory system and lung, respectively. A linear V-P relationship of the chest wall was observed during the control condition and after separation from CPB. Four hours later, no further increases in the pressure values corresponding to Pflex were observed on the inspiratory V-P curves of the respiratory system and lung, whereas the UIP occurred at a pressure of 35.6+/-9.1 and 29.7+/-8.4 cm H2O, respectively. A UIP was present on the V-P curve of the chest wall at a volume of 0.77+/-0.02 L. Seven hours after separation from CPB, the inspiratory V-P curves of the respiratory system, chest wall, and lung returned to normal. CONCLUSIONS: Sternotomy and CPB produced immediate changes in lung mechanics. Chest wall mechanics were affected only 4 hrs after sternotomy. Seven hours after disconnection from CPB, all mechanics had returned to normal.

Adult↗
PubMed1999

Role of endothelial cell extracellular signal-regulated kinase1/2 in urokinase-type plasminogen activator upregulation and in vitro angiogenesis by fibroblast growth factor-2.

Downstream signaling triggered by the binding of fibroblast growth factor-2 (FGF2) to its tyrosine-kinase receptors involves the activation of mitogen-activated protein kinase kinase (MEK) with consequent phosphorylation of extracellular signal-regulated kinases (ERKs). Here we demonstrate that FGF2 induces ERK1/2 activation in bovine aortic endothelial (BAE) cells and that the continuous presence of the growth factor is required for sustained ERK1/2 phosphorylation. This is prevented by the MEK inhibitors PD 098059 and U0126, which also inhibit FGF2-mediated upregulation of urokinase-type plasminogen activator (uPA) and in vitro formation of capillary-like structures in three-dimensional type I collagen gel. Various FGF2 mutants originated by deletion or substitution of basic amino acid residues in the amino terminus or in the carboxyl terminus of FGF2 retained the capacity to induce a long-lasting activation of ERK1/2 in BAE cells. Among them, K128Q/R129Q-FGF2 was also able to stimulate uPA production and morphogenesis whereas R129Q/K134Q-FGF2 caused uPA upregulation only. In contrast, K27, 30Q/R31Q-FGF2, K128Q/K138Q-FGF2 and R118,129Q/K119,128Q-FGF2 exerted a significant uPA-inducing and morphogenic activity in an ERK1/2-dependent manner only in the presence of heparin. Furthermore, no uPA upregulation and morphogenesis was observed in BAE cells treated with the deletion mutant (delta)27-32-FGF2 even in the presence of soluble heparin. Thus, mutational analysis of FGF2 dissociates the capacity of the growth factor to induce a persistent activation of ERK1/2 from its ability to stimulate uPA upregulation and/or in vitro angiogenesis. In conclusion, the data indicate that ERK1/2 phosphorylation is a key step in the signal transduction pathway switched on by FGF2 in endothelial cells. Nevertheless, a sustained ERK1/2 activation is not sufficient to trigger uPA upregulation and morphogenesis. FGF2 mutants may represent useful tools to dissect the signal transduction pathway(s) mediating the complex response elicited by an angiogenic stimulus in endothelial cells.

Amino Acid Sequence↗
PubMed1999

In vivo angiogenic activity of urokinase: role of endogenous fibroblast growth factor-2.

In vitro experimental evidences suggest that the proteolytic degradation of the extracellular matrix (ECM) by activation of the urokinase-type plasminogen activator (uPA)/plasmin system may affect growth factor activity and bioavailability. However, no direct in vivo observations were available to support this hypothesis. Here we demonstrate that endothelial GM 7373 cells overexpressing human uPA (uPA-R5 cells) cause the release of (125)I-labeled fibroblast growth factor-2 (FGF2) from endothelial ECM in a plasmin-dependent manner. Accordingly, uPA-R5 cells are angiogenic in vivo when applied on the top of the chorioallantoic membrane (CAM) of the chick embryo. In contrast, mock-transfected Neo2 cells are unable to release ECM-bound (125)I-FGF2 and are poorly angiogenic. Neovascularization elicited by uPA-R5 cells is significantly reduced by neutralizing anti-FGF2 antibodies to values similar to those observed in Neo2 cell-treated CAMs. Accordingly, purified human uPA stimulates neovascularization of the CAM in the absence of an inflammatory response. The angiogenic activity of uPA is significantly inhibited by neutralizing anti-FGF2 antibodies or by pretreatment with phenylmethylsulfonyl fluoride. The non-catalytic, receptor-binding amino-terminal fragment of uPA is instead non angiogenic. Taken together, the data indicate that uPA is able to induce angiogenesis in vivo via a plasmin-dependent degradation of ECM that causes the mobilization of stored endogenous FGF2.

Allantois↗
PubMed1998

The basic domain in HIV-1 Tat protein as a target for polysulfonated heparin-mimicking extracellular Tat antagonists.

Heparin binds extracellular HIV-1 Tat protein and modulates its HIV long terminal repeat (LTR)-transactivating activity (M. Rusnati, D. Coltrini, P. Oreste, G. Zoppetti, A. Albini, D. Noonan, F. d'Adda di Fagagna, M. Giacca, and M. Presta (1997) J. Biol. Chem. 272, 11313-11320). On this basis, the glutathione S-transferase (GST)-TatR49/52/53/55/56/57A mutant, in which six arginine residues within the basic domain of Tat were mutagenized to alanine residues, was compared with GST-Tat for its capacity to bind immobilized heparin. Dissociation of the GST-TatR49/52/53/55/56/57A.heparin complex occurred at ionic strength significantly lower than that required to dissociate the GST-Tat.heparin complex. Accordingly, heparin binds immobilized GST-Tat and GST-TatR49/52/53/55/56/57A with a dissociation constant equal to 0.3 and 1.0 microM, respectively. Also, the synthetic basic domain Tat-(41-60) competes with GST-Tat for heparin binding. Suramin inhibits [3H]heparin/Tat interaction, 125I-GST-Tat internalization, and the LTR-transactivating activity of extracellular Tat in HL3T1 cells and prevents 125I-GST-Tat binding and cell proliferation in Tat-overexpressing T53 cells. The suramin derivative 14C-PNU 145156E binds immobilized GST-Tat with a dissociation constant 5 times higher than heparin and is unable to bind GST-TatR49/52/53/55/56/57A. Although heparin was an antagonist more potent than suramin, modifications of the backbone structure in selected suramin derivatives originated Tat antagonists whose potency was close to that shown by heparin. In conclusion, suramin derivatives bind the basic domain of Tat, prevent Tat/heparin and Tat/cell surface interactions, and inhibit the biological activity of extracellular Tat. Our data demonstrate that tailored polysulfonated compounds represent potent extracellular Tat inhibitors of possible therapeutic value.

Animals↗
PubMed1997

Effects of proportional assist ventilation on inspiratory muscle effort in patients with chronic obstructive pulmonary disease and acute respiratory failure.

BACKGROUND: Acute respiratory failure may develop in patients with chronic obstructive pulmonary disease because of intrinsic positive end-expiratory pressure (PEEPi) and increased resistive and elastic loads. Proportional assist ventilation is an experimental mode of partial ventilatory support in which the ventilator generates flow to unload the resistive burden (flow assistance: FA) and volume to unload the elastic burden (volume assistance: VA) proportionally to inspiratory muscle effort, and PEEPi can be counterbalanced by application of external PEEP. The authors assessed effects of proportional assist ventilation and optimal ventilatory settings in patients with chronic obstructive pulmonary disease and acute respiratory failure. METHODS: Inspiratory muscles and diaphragmatic efforts were evaluated by measurements of esophageal, gastric, and transdiaphragmatic pressures. Minute ventilation and breathing patterns were evaluated by measuring airway pressure and flow. Measurements were performed during spontaneous breathing, continuous positive airway pressure, FA, FA+PEEP, VA, VA+PEEP, FA+VA, and FA+VA+PEEP. RESULTS: FA+PEEP provided the greatest improvement in minute ventilation (89 +/- 3%) and dyspnea (62 +/- 2%). The largest reduction in pressure time product per breath of the respiratory muscles and diaphragm (44 +/- 3% and 33 +/- 2%, respectively) also was observed during FA+PEEP condition. When VA was added to this setting, a reduction in respiratory rate (50 +/- 3%), an increase in inspiratory time (102 +/- 6%), and a further reduction in pressure time product per minute (65 +/- 2% and 64% for the respiratory muscles and diaphragm, respectively) was observed. However, values of pressure time product per liter of minute ventilation during FA+VA+PEEP did not differ with those observed during FA+PEEP condition. Worsening of patient-ventilator interaction and breathing asynchrony occurred when VA was implemented. CONCLUSIONS: Application of PEEP to counterbalance PEEPi and FA to unload the resistive burden provided the optimal conditions in such patients. Ventilator over-assistance and patient-ventilator asynchrony was observed when VA was added to this setting. The clinical use of proportional assist ventilation should be based on continuous measurements of respiratory mechanics.

Acute Disease↗
PubMed1997

Upregulation of urokinase-type plasminogen activator by endogenous and exogenous HIV-1 Tat protein in tumour cell lines derived from BK virus/tat-transgenic mice.

OBJECTIVE: To demonstrate that Tat modulates the plasminogen-dependent proteolytic activity of tumour cell lines derived from BK virus (BKV)/tat-transgenic mice by affecting the production of plasminogen activators (PA) and the PA inhibitor (PAI)-1 and to demonstrate that this occurs through mechanism(s) that are distinct from those responsible for transactivating activity of extracellular Tat. DESIGN AND METHODS: To assess whether endogenous Tat is responsible for PA activity in T53 adenocarcinoma cells, cell cultures were transfected with antisense Tat cDNA and evaluated for cell-associated PA activity by a plasmin chromogenic assay. The assay was also used to evaluate PA activity in T53 cells and T111 leiomyosarcoma cells stimulated by extracellular Tat. The type(s) of PA produced were identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis zymography. The levels of PAI-1 were evaluated by Western blotting. Tat transactivating activity was measured by a chloramphenicol acetyltransferase (CAT) enzyme-linked immunosorbent assay in HL3T1 cells containing integrated copies of an HIV-1 long terminal repeat (LTR)-CAT plasmid. RESULTS: Transfection of T53 cells with antisense Tat cDNA results in the decrease of Tat production and PA activity. Exogenously added Tat increases PA levels in T53 and in T111 cells. PA activity was identified as urokinase-type PA (uPA). Tat also increases the production of PAI-1 in T111 but not in T53 cells. Chloroquine and heparin have different affects on the LTR-CAT-transactivating and the PA-inducing activities of Tat. The fusion protein glutathione-S-transferase-Tat and the mutant Tat-1e, lacking the second Tat exon, cause LTR-CAT transactivation without stimulating uPA upregulation. CONCLUSIONS: Tat affects the fibrinolytic activity of tumour cell lines derived from BKV/tat-transgenic mice by modulating the production of both uPA and PAI-1 via autocrine and paracrine mechanisms of action. The capacity of Tat to modulate the plasminogen-dependent proteolytic activity of these tumour cell lines may contribute to their metastatic potential. The uPA-inducing activity of Tat depends upon specific biological and structural features of the Tat protein that are distinct from those responsible for its LTR-CAT-transactivating activity, suggesting distinct mechanisms of induction for the two biological responses.

Animals↗
PubMed1997

Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome: role of abdominal distension.

Recent data have suggested that the elastic properties of the chest wall (CW) may be compromised in patients with ARDS because of abdominal distension (4). We partitioned CW and lung (L) mechanics, assessed the role of abdominal distension, and verified whether the underlying disease responsible for ARDS affects the impairment of respiratory mechanics. Volume-pressure (V-P) curves (interrupter technique) were assessed in nine patients with surgical ARDS and nine patients with medical ARDS. Relative to nine patients undergoing heart surgery, V-P curves of the respiratory system (rs) and L of patients with surgical or medical ARDS showed a rightward displacement. V-P curves of the CW and the L showed an upward concavity in patients with medical ARDS and a downward concavity in patients with surgical ARDS. Although the CW and the abdomen (abd) V-P curves in patients with medical ARDS were similar to those obtained in patients undergoing heart surgery, they showed a rightward shift and a downward flattening in patients with surgical ARDS. In five of these patients, a reduction in static end-inspiratory pressure of the abd (69+/-4%), rs (30+/-3%), CW (41+/-2%), and L (27+/-3%) was observed after abdominal decompression for acute bleeding. Abdominal decompression therefore caused an upward and leftward shift of the V-P curves of the respiratory system, chest wall, lung, and abdomen. In conclusion we showed that impairment of the elastic properties of the respiratory system may vary with the underlying disease responsible for ARDS. The flattening of the V-P curve at high pressures observed in some patients with ARDS may be due to an increase in chest wall elastance related to abdominal distension. These observations have implications for the assessment and ventilatory management of patients with ARDS.

Abdomen↗
PubMed1996

Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure.

OBJECTIVE: To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi). DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Seven mechanically ventilated flow-limited COPD patients (PEEPi = 9.7 +/- 1.3 cmH2O, mean +/- SD) with acute respiratory failure. INTERVENTION: Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH2O). MEASUREMENTS AND RESULTS: Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH2O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right end-diastolic ventricular volume index (RVEDVI) (r = 0.61; p < 0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r = -55; p < 0.001), but no with PEEPi,cw (r = -0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur. CONCLUSIONS: In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.

Acute Disease↗
PubMed1996

Auto-positive end-expiratory pressure and dynamic hyperinflation.

PEEP is indicated in patients with COPD only to unload the respiratory muscles from the auto-PEEP resulting from expiratory flow limitation. If auto-PEEP is not caused by flow limitation, application of PEEP will cause further hyperinflation, worsening respiratory mechanics, muscle activity, and hemodynamics. To assess the presence of expiratory flow limitation correctly, to measure auto-PEEP correctly, and to identify the maximal PEEP level to be used, measurements of flow and opening pressure must be obtained during a brief period of suspended respiratory muscle activity (obtained by sedation) with the patient's own breathing pattern reproduced accurately.

Humans↗
PubMed1996

Patient-ventilator interaction during acute hypercapnia: pressure-support vs. proportional-assist ventilation.

The objective of this study was to compare patient-ventilator interaction during pressure-support ventilation (PSV) and proportional-assist ventilation (PAV) in the course of increased ventilatory requirement obtained by adding a dead space in 12 patients on weaning from mechanical ventilation. With PSV, the level of unloading was provided by setting the inspiratory pressure at 20 and 10 cmH2O, whereas with PAV the level of unloading was at 80 and 40% of the elastic and resistive load. Hypercapnia increased (P < 0.001) tidal swing of esophageal pressure and pressure-time product per breath at both levels of PSV and PAV. During PSV, application of dead space increased ventilation (VE) during PSV (67 +/- 4 and 145 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001). This was due to a relevant increase in respiratory rate (48 +/- 4 and 103 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001), whereas the increase in tidal volume (VT) played a small role (13 +/- 1 and 21 +/- 2% during 20 and 10 cmH2O PSV, respectively, P < 0.001). With PAV, the increase in VE consequent to hypercapnia (27 +/- 3 and 64 +/- 4% during 80 and 40% PAV, respectively, P < 0.001) was related to the increase in VT (32 +/- 1 and 66 +/- 2% during 80 and 40% PAV, respectively, P < 0.001), respiratory rate remaining unchanged. The increase in pressure-time product per minute and per liter consequent to acute hypercapnia and the sense of breathlessness were significantly (P < 0.001) higher during PSV than during PAV. Our data show that, after hypercapnic stimulation of the respiratory drive, the capability to increase VE through changes in VT modulated by variations in inspiratory muscle effort is preserved only during PAV; the compensatory strategy used to increase VE during PSV requires greater muscle effort and causes more pronounced patient discomfort than during PAV.

Adult↗
PubMed1996

Chest wall and lung contribution to the elastic properties of the respiratory system in patients with chronic obstructive pulmonary disease.

Conflicting data are available on the relative contribution of the chest wall (cw) to the intrinsic positive end-expiratory pressure of the total respiratory system (PEEPi,rs) in patients with chronic obstructive pulmonary disease (COPD). In order to assess the chest wall and lung contribution to the elastic properties of the respiratory system in COPD patients during acute ventilatory failure, using the "interrupter technique", static inflation volume-pressure (V-P) curves of the total respiratory system (rs), lung (L) and cw were obtained in seven mechanically-ventilated COPD patients during application of zero end-expiratory pressure (ZEEP) and different levels (0-15 cmH2O) of PEEP. On ZEEP, PEEPi,rs was present in all patients (range 10.5-13.1 cmH2O), to which PEEPi,cw and PEEPi,L contributed 17 +/- 2 and 83 +/- 1%, respectively. The static V-P curves of the rs, L, and cw on ZEEP were concave toward the horizontal axis, indicating that elastance increased with inflating volume. Application of PEEP did not affect lung and chest wall mechanics until PEEP levels exceeding 90% of PEEPi,cw on ZEEP (critical value of PEEP (Pcrit)). At PEEP levels higher than Pcrit, and relative to the V-P curves on ZEEP, we observed that: 1) the V-P curve of the rs showed an initial shift along the curve on ZEEP followed by a downward displacement with inflating volume; 2) the V-P curve of the L was shifted along the curve on ZEEP throughout inflating volume; and 3) the V-P curve of the cw was initially displaced along the curve on ZEEP, whilst a downward displacement appeared at higher lung volume. In conclusion, our data show that, in chronic obstructive pulmonary disease patients with flow limitation, the increase in pleural pressure does not make a significant contribution to the intrinsic positive end-expiratory pressure of the total respiratory system. However, during tidal ventilation, a substantial increase in elastance of the chest wall is present. The critical values of positive end-expiratory pressure below which there are no changes in chest wall and lung mechanics amount to 90% of the total PEEPi,rs on ZEEP. Positive end-expiratory pressure levels higher than such critical value cause important alterations of the elastic properties of the lung and chest wall.

Aged↗
PubMed1995

Silicone breast implants: the role of immune system on capsular contracture formation.

We evaluated the role of the immune system in the pathogenesis of the periprosthetic capsular contracture, the most frequently occurring complication following the implant of silicone prostheses. Peripheral blood samples from 22 patients with silicone-gel-filled implants were examined. In all cases a capsule was felt by palpation, and it was classified according to the Baker scale. Ten patients (group 1) had a Baker 2 contracture, and 12 (group 2) had severe contracture rated 3 and 4. The cells positive to antigens CD3, CD4, CD8, HLA-DR, CD19, CD25, CD57, CD16, and CD14, and the cytotoxic activity of the lymphocytes on target cells K562 were assessed by cytofluorimetric analysis. At time 0 there were no statistically significant differences between patients and normal subjects, nor between the two groups. At 48 h, the group 2 patients had a number/mm3 of cells CD57 + significantly higher than both group 1 and control group (P < .05). In group 1 patients, the cytotoxic activity was similar to that of normal subjects, whereas in group 2 it was significantly increased, in respect to both the controls (P < .05) and group 1 (P < .001). In all groups, the contact of the lymphocytes with the silicone extract did not modify either the antigen expression or the lymphocyte functional activity. On the basis of these results we hypothesize the involvement of the immune system in the formation of the capsular contracture around the prosthesis.

Adult↗
PubMed1995

Assessment of viability and proliferation of in vivo silicone-primed lymphocytes after in vitro re-exposure to silicone.

The functional response of peripheral blood lymphocytes isolated from 22 patients with silicone gel-filled breast implants was assessed after in vitro re-exposure to silicone. Using cell culture test methods to quantify proliferation and viability and/or activation of lymphocyte microcultures, i.e., the uptake of tritiated thymidine (3H-TdR uptake test) and the reduction of formazan salts (MTT assay), interesting data were obtained. Peripheral blood lymphocytes purified from patients wearing silicone gel-filled breast implants react in vitro to silicone showing a statistically significant increase of both proliferation and viability, while healthy subjects do not respond on in vitro exposure to silicone. Differences resulted even more statistically significant when patients were divided into two groups depending on the type of surgery they underwent: patients with breast augmentation for aesthetic reasons seem to have an increased responsiveness in vitro to silicone compared to patients who experienced a reconstructive surgery of the breast. Although they are still preliminary, being referred to a limited population, these results suggest that the lymphocytes of patients with silicone gel-filled breast implants could be sensitized in vivo toward silicone; the re-exposure of these cells to silicone leads to a higher functional response which could be looked for by using quantitative in vitro test methods.

Adult↗
PubMed1995

Inspiratory effort and measurement of dynamic intrinsic PEEP in COPD patients: effects of ventilator triggering systems.

OBJECTIVE: To investigate effects of ventilator triggering systems (pressure and flow triggering: PT and FT) on measurement of dynamic intrinsic PEEP (PEEPidyn) and patient-ventilator interaction in patients with chronic obstructive pulmonary disease during weaning from mechanical ventilation. DESIGN: Prospective study. SETTING: Medical/surgical intensive care unit of an academic hospital. PATIENTS AND PARTICIPANTS: 6 COPD patients with acute respiratory failure ready to wean. MEASUREMENTS: We measured flow, airway opening, esophageal and gastric pressures. Minute ventilation, breathing pattern and pressure time product (PTP) of the respiratory muscles and of the diaphragm were obtained during spontaneous ventilation through a mechanical ventilator (Puritan-Bennett 7200ae). Two triggering systems, namely PT and FT, were evaluated. RESULTS: The inspiratory muscles effort necessary to overcome the triggering system overestimated PEEPidyn measurement of an amount equal to 49 +/- 2 and 58 +/- 3% during respectively pressure and flow triggering. FT increased tidal volume and minute ventilation and decrease PTP/b and PTP/min of the respiratory muscles and diaphragm. CONCLUSIONS: To correctly measure PEEPidyn, the inspiratory effort produced to overcome PEEPi and to trigger the ventilator must be discriminated. Application of flow triggering requires less effort to initiate inspiration and provide a positive end-expiratory pressure level that is able to unload the respiratory muscles by reducing PEEPi. With flow triggering higher minute ventilation are obtained in COPD patients during the weaning phase.

Acute Disease↗
PubMed1995

Cardiorespiratory effects of positive end-expiratory pressure during progressive tidal volume reduction (permissive hypercapnia) in patients with acute respiratory distress syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the ventilatory approach is based on tidal volume (VT) of 10-15 ml/kg and positive end-expiratory pressure (PEEP). To avoid further pulmonary injury, decreasing VT and allowing PaCO2 to increase (permissive hypercapnia) has been suggested. Effects of 10 cmH2O of PEEP on respiratory mechanics, hemodynamics, and gas exchange were compared during mechanical ventilation with conventional (10-15 ml/kg) and low (5-8 ml/kg) VT. METHODS: Nine sedated and paralyzed patients were studied. VT was decreased gradually (50 ml every 20-30 min). Static volume-pressure (V-P) curves, hemodynamics, and gas exchange were measured. RESULTS: During mechanical ventilation with conventional VT, V-P curves on PEEP 0 (ZEEP) exhibited an upward convexity in six patients reflecting a progressive reduction in compliance with inflating volume, whereas PEEP resulted in a volume displacement along the flat part of this curve. After VT reduction, V-P curves in the same patients showed an upward concavity, reflecting progressive alveolar recruitment with inflating volume, and application of PEEP resulted in alveolar recruitment. The other three patients showed a V-P curve with an upward concavity; VT reduction increased this concavity, and application of PEEP induced greater alveolar recruitment than during conventional VT. With PEEP, cardiac index decreased by, respectively, 31% during conventional VT and 11% during low VT (P < 0.01); PaO2 increased by 32% and 71% (P < 0.01), respectively, whereas right-to-left venous admixture (Qs/Qt) decreased by 11% and 40%, respectively (P < 0.01). The greatest values of PaO2, static compliance, and oxygen delivery and the lowest values of Qs/Qt (best PEEP) were obtained during application of PEEP with low VT (P < 0.01). CONCLUSIONS: Although PEEP induced alveolar hyperinflation in most patients during mechanical ventilation with conventional VT, at low VT, there appeared to be a significant alveolar collapse, and PEEP was able to expand these units, improving gas exchange and hemodynamics.

Female↗