Sodium nitroprusside for advanced heart failure. A metanalysis of literature data.

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

Iatrogenic atrial septal defect does not affect acute hemodynamic modifications after transcatheter edge-to-edge repair in patients with functional mitral regurgitation.

OBJECTIVE: The correction of functional mitral regurgitation (FMR) with transcatheter edge-to-edge repair (TEER) can favorably affect patients' hemodynamic profile. However, the procedure requires inter-atrial trans-septal access and the hemodynamic relevance of the residual iatrogenic atrium septal defect (iASD) is still debated. This study aimed at investigating the hemodynamic modifications during TEER with MitraClip, before and after the iASD creation, in patients with heart failure with reduced ejection fraction (HFrEF) and severe FMR. METHODS: Thirty-nine HFrEF patients with 3+ or 4+/4+ FMR were included. Right heart catheterization was performed at baseline after general anesthesia induction and at the end of TEER, both before and after removing the device guiding catheter. RESULTS: Compared with baseline, MitraClip positioning was followed by a significant immediate improvement in cardiac output (respectively: 3.36 vs 5.05 ml/min), pulmonary artery wedge pressure (23.7 vs 18.2 mmHg), mean pulmonary artery pressure (34.4 vs 27.7 mmHg) and pulmonary vascular resistance (3.6 vs 2.2 Wood Units) (all p < 0.001). No further significant modifications occurred after removing the device guiding catheter. CONCLUSIONS: Our data suggest that the acute hemodynamic modifications after TEER are not influenced by the induction of iASD in patients with FMR.

Secretome profile of Cellulomonas sp. B6 growing on lignocellulosic substrates.

AIMS: Lignocellulosic biomass deconstruction is a bottleneck for obtaining biofuels and value-added products. Our main goal was to characterize the secretome of a novel isolate, Cellulomonas sp. B6, when grown on residual biomass for the formulation of cost-efficient enzymatic cocktails. METHODS AND RESULTS: We identified 205 potential CAZymes in the genome of Cellulomonas sp. B6, 91 of which were glycoside hydrolases (GH). By secretome analysis of supernatants from cultures in either extruded wheat straw (EWS), grinded sugar cane straw (SCR) or carboxymethylcellulose (CMC), we identified which proteins played a role in lignocellulose deconstruction. Growth on CMC resulted in the secretion of two exoglucanases (GH6 and GH48) and two GH10 xylanases, while growth on SCR or EWS resulted in the identification of a diversity of CAZymes. From the 32 GHs predicted to be secreted, 22 were identified in supernatants from EWS and/or SCR cultures, including endo- and exoglucanases, xylanases, a xyloglucanase, an arabinofuranosidase/ß-xylosidase, a ß-glucosidase and an AA10. Surprisingly, among the xylanases, seven were GH10. CONCLUSIONS: Growth of Cellulomonas sp. B6 on lignocellulosic biomass induced the secretion of a diverse repertoire of CAZymes. SIGNIFICANCE AND IMPACT OF THE STUDY: Cellulomonas sp. B6 could serve as a source of lignocellulose-degrading enzymes applicable to bioprocessing and biotechnological industries.

Translating the combination of gene therapy and tissue engineering for treating recessive dystrophic epidermolysis bullosa.

The combination of gene therapy and tissue engineering is one of the most promising strategies for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a rare genetic disease characterised by mutations in the COL7A1 gene, encoding type VII collagen (COLVII), which forms anchoring fibrils at the dermal-epidermal junction of the skin. This disease causes severe blistering and only palliative treatments are offered. In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up. As a high transduction efficiency into fibroblasts and/or keratinocytes seems to be a prerequisite for a robust and sustained correction of RDEB, different envelope pseudotyped retroviral vectors and the transduction enhancer EF-C were tested. When green fluorescent protein (GFP) was used as a reporter gene to evaluate the retroviral-mediated gene transfer, the fibroblast infection efficiency was 30 % higher with the Ampho pseudotyped vector as compared with the other pseudotypes. At least a 3.1-fold and a 1.3-fold increased transduction were obtained in fibroblasts and keratinocytes, respectively, with EF-C as compared with polybrene. A continuous and intense deposit of haemagglutinin (HA)-COLVII was observed at the dermal-epidermal junction of self-assembled TESs made of cells transduced with a HA-tagged COL7A1 vector. Furthermore, HA-tagged basal epidermal cells expressing keratin 19 were observed in TESs, suggesting stem cell transduction. This approach could be a valuable therapeutic option to further develop, in order to improve the long-term life quality of RDEB patients.

Left atrial dilatation in systolic heart failure: a marker of poor prognosis, not just a buffer between the left ventricle and pulmonary circulation.

BACKGROUND: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF). METHODS: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure. RESULTS: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p < 0.0001 for all). At multivariate analysis, LAD was positively associated with sPAP (p < 0.0001) independently of EF, RMP, and FMR. Analogously, LAD (p < 0.05) was associated with more severe symptoms and worse prognosis after adjustment for LV function and FMR. CONCLUSION: LA dilation was positively associated with sPAP independently of EF, RMP, and FMR. This highlights that LA size should be considered a marker of the severity of the disease.

Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

Effects on survival of loop diuretic dosing in ambulatory patients with chronic heart failure using a propensity score analysis.

OBJECTIVE: To ascertain whether increasing doses of orally administered furosemide are associated with impaired survival in outpatients with chronic heart failure (CHF) and left ventricular (LV) systolic dysfunction. METHODS: Transthoracic echo-Doppler examination was carried out at baseline in 813 consecutive CHF outpatients with LV ejection fraction ≤ 45%. The total daily dose of furosemide was assessed for each patient. Chronic kidney disease (CKD) was defined by a glomerular filtration rate < 60 ml/min/1.73 m(2). The end-point was all-cause mortality. To control the prognostic effect of furosemide for the propensity of using high doses of the drug, the Cox model was stratified by the propensity score, itself computed from a multivariable logistic model. Mean follow up was 44 months. RESULTS: After stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide dose (HR 1.38, 95% CI 1.14-1.68, p < 0.001). A daily dose of 50 mg was identified as the best threshold value to predict a high risk of death within 3 years with an area under the ROC curve of 0.68 (95% CI 0.64-0.72). Increasing doses of furosemide were associated with an increased risk of death regardless of LV filling pattern, CKD and background therapy with ACE-inhibitors or beta-blockers. CONCLUSIONS: In outpatients with CHF, after stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide daily dose. A threshold furosemide dose of 50 mg was related with the worse outcome.

Paediatric nurses' perception of the child-family dyad's autonomy in managing a chronic disease situation: the experience of an Italian paediatric department.

INTRODUCTION: Chronically ill patients have to take several medications and non-adherence to treatment can lead to severe and negative outcomes. Therefore, several interventions are suggested in literature to improve adherence rates in clinical practice. Adherence to treatment can be particularly troublesome in adolescents, who strive for autonomy and self-care independence. Literature suggests that improving adherence is useful to guarantee positive outcomes and reduce costs. AIM: To explore how nurses perceived autonomy in parents, adolescents, and children related to the management of chronic disease. MATERIALS AND METHODS: A qualitative study including 1 focus group and 7 semi-structured interviews conducted between September 2011 and October 2011. The qualitative date were analysed with the thematic analysis method. The sample included 12 paediatric nurses working in a Children's Cystic Fibrosis Unit and Neuromuscular Disease Unit. RESULTS: The 5 main categories that emerged from this qualitative study after he process of categorization were: 'Changes in daily lifestyle', 'Nurses' attitude towards educating the dyad', 'Adolescence and transition', 'Parents' attitudes towards chronic disease', and 'Availability of information'. DISCUSSION: Correct information and education is crucial for families who have a chronically ill child. Internet can be a misleading source of information and provide wrong information also in relation to prevention.

The tailored medical therapy in patients with advanced heart failure referred for cardiac transplantation.

INTRODUCTION: Optimal pharmacologic management of heart transplant (HT) candidates is required prior to evaluation so as to obtain a reliable prognostic stratification and to address the donor shortage. The aim of this study was to determine whether a tailored medical approach was effectively achieved before HT waiting list enrollment. MATERIALS AND METHODS: This study concerned 40 consecutive patients referred for HT evaluation who underwent a clinical assessment, including hemodynamic, echocardiographic, and brain natriuretic peptide determinations. Medical therapy was optimized according to the clinical assessment to improve neurohormonal and hemodynamic profiles. We analyzed the distribution of the different drugs between the first and the following evaluation to demonstrate whether a significant improvement of medical therapy could be achieved in advanced chronic heart failure (ACHF). RESULTS: The mean age was 53 years, including 93% males. The etiology of disease was ischemic in 40% and idiopathic in 45%. The mean left ventricular ejection fraction was 23%, mean values of hemodynamic data were cardiac index (CI) 2+/-0.6 L/min/m(2), mean pulmonary arterial pressure (mPAP) 30+/-10 mm Hg, wedge pressure (PWP) 23+/-8 mm Hg; mean BNP was 618 pg/mL. Median follow-up was 397 days; 82% of candidates underwent HT waiting-list enrollment. The medical treatment was modified as follows: beta-blockers were introduced or uptitrated in 32%, angiotensin receptor blockers (ARB) were introduced in 7.5%, spironolactone was started in 42%, nitrates were introduced in 20%, and diuretics were uptitrated in 35% of patients. CONCLUSION: In patients with ACHF referred for HT, a further effort in the assessment of the medical treatment is strongly recommended.

Cigarette smoking and hypertension influence nitric oxide release and plasma levels of adhesion molecules.

Progression of atherosclerosis is currently believed to involve interactions between leukocytes and vascular endothelium. Epidemiological risk factors for atherosclerosis such as hypertension and smoking are known to cause endothelial dysfunction, which is an early event in the atherosclerotic process; they also may be considered in the light of their effects on adhesion molecule expression and release. Little is known about the additive effect between these two risk factors on endothelial adhesion molecule expression and nitric oxide release. Soluble adhesion molecules and the nitric oxide were quantified in smoking hypertensive patients in comparison to those from patients with hypertension alone. Cotinine, a stable metabolite of nicotine, has been used to identify smokers. One hundred and three hypertensive patients were selected: 51 smokers (plasma cotinine levels >25 ng/ml) and 52 non-smokers. Plasma concentrations of soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-I) were quantified with ELISA methods. Plasma concentration of nitric oxide metabolites was measured by HPLC, whilst plasma concentration of cotinine was measured by RIA. Significant increases of sICAM-1 and sVCAM-1 were demonstrated in smokers (p<0.001 and p<0.05, respectively). In the same patients, a positive significant correlation between sVCAM-1 and plasma cotinine levels was observed (p<0.002). Nitric oxide metabolites were reduced significantly (p<0.04) in smokers. In conclusion, our data show that the two risk factors, smoking and hypertension, are additive risk factors in generating endothelial dysfunction and vascular damage, which plays a key role in atherogenesis.

Doppler velocimetry in superior vena cava provides useful information on the right circulatory function in patients with congestive heart failure.

BACKGROUND: Although flow velocities curves recorded with pulsed-wave Doppler in systemic vein are known to provide functional data on the right circulatory function, little information is available on the relationship between right heart filling dynamics and right ventricular function. METHODS: Consecutive patients with chronic heart failure due to severe systolic left ventricular dysfunction and in sinus rhythm underwent echocardiography and right heart catheterization. In the initial part of the study, the hemodynamic correlates of different flow velocity patterns recorded into the superior vena cava were evaluated in 120 patients. The accuracy of the prediction of different right heart hemodynamic profiles by means of the different venous flow patterns was then prospectively tested in a subsequent series of 86 patients. RESULTS: The venous flow pattern was closely related to right heart hemodynamics. A normal Doppler pattern identified patients with normal right heart hemodynamics (sensitivity 86%, specificity 78%); a "predominant systolic wave" pattern identified patients with a reduced thermodilution-derived right ventricular ejection fraction (< 30%) and normal or slightly elevated right atrial pressure (< or = 8 mmHg) (sensitivity 69%, specificity 81%); a "predominant diastolic wave" pattern identified patients with a reduced right ventricular ejection fraction (< 3 0%) and elevated right atrial pressure (> 8 mmHg) (sensitivity 52%, specificity 95%). The observed and the predicted hemodynamic profiles turned out to be concordant in 80% of patients. CONCLUSIONS: The analysis of the flow velocity pattern into the superior vena cava is a useful tool to estimate the extent of the right circulatory impairment in patients with congestive heart failure.

Echocardiographic evolution of left ventricular and left atrial thrombi in a patient with left ventricular dysfunction due to alcoholic cardiomyopathy, chronic atrial fibrillation and multiple non-fatal systemic embolisms.

The echocardiographic characteristics and evolution of multiple pedunculated left atrial and left ventricular intracavitary thrombi in a patient with alcoholic cardiomyopathy are reported. The patient had a long history of left ventricular dysfunction and atrial fibrillation but the referring physician had not prescribed anticoagulant prophylaxis. Multiple, non-fatal, systemic embolizations occurred during hospitalization and echocardiography was used to monitor the effect of the anticoagulant therapy on the remodelling and final dissolution of intracavitary thrombi.

Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure.

OBJECTIVES: We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND: Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS: Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS: During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS: These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.

[Non-invasive evaluation of the hemodynamic profile in patients with heart failure: estimation of pulmonary arterial pressure]. / Valutazione non invasiva del profilo emodinamico nel paziente con scompenso cardiaco: stima della pressione arteriosa polmonare.

Continuous-wave Doppler echocardiography is an accurate method for the non-invasive estimation of pulmonary artery pressure because the pressure gradient across a regurgitant valve can be estimated accurately by measuring the high flow velocity of the regurgitant jet and by applying the simplified Bernoulli equation. Measurable tricuspid and/or pulmonary regurgitation can be observed in a great percentage of patients with heart failure (approximately 90% of patients if the examination is performed by an experienced sonographer) and the method has a wide clinical applicability. Recently, new attention has been focused on the possibility of evaluating the right ventricular function by echocardiography. Although the measurement of the volumes of this cardiac chamber is undoubtedly difficult with ultrasound (as it is with most imaging techniques), it must be recognized that echocardiography allows for the measurement of simple M-mode and two-dimensional parameters which are extremely useful in the prognostic stratification of patients with congestive heart failure.

Five-minute recording of heart rate variability in severe chronic heart failure: correlates with right ventricular function and prognostic implications.

BACKGROUND: In advanced chronic heart failure (CHF), correlation between heart rate variability (HRV) and parameters of disease severity is still unclear. A reduced HRV has been related to left but not to right ventricular function parameters. Moreover, the prognostic role of spectral measures is not fully defined. We sought to assess HRV by using a short electrocardiographic recording in ambulatory patients with severe CHF to investigate the relation of HRV with clinical neurohormonal and hemodynamic parameters and to determine its predictive prognostic power. METHODS AND RESULTS: HRV was obtained from 5-minute electrocardiographic recordings in 75 ambulatory patients with CHF referred for heart transplantation screening. Standard frequency-domain parameters (total power, low-frequency power, and high-frequency power) were calculated. Prognostic value of these autonomic markers and their correlation with clinical and instrumental parameters were also assessed. A low low-frequency/high-frequency ratio was an independent predictor of cardiac events (P =.015). No correlation was found between New York Heart Association class and HRV, whereas significant correlations were identified between norepinephrine plasma levels, several hemodynamic parameters, and spectral measures (P < or =.03). A reduced HRV, particularly a low-frequency power reduction (P =.000), was highly related to indexes of right ventricular dysfunction. CONCLUSIONS: The current data indicate that spectral analysis of HRV, calculated from short electrocardiographic recordings, may represent a simple but effective means contributing to risk stratification of patients with severe CHF. Autonomic information obtained from this analysis suggests that right ventricular dysfunction may be a critical element determining autonomic imbalance in patients with severe CHF.

Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy.

The prognostic value of ultrasound evaluation of right ventricular (RV) performance in patients with congestive heart failure (CHF) is still a matter of investigation. We studied 140 consecutive patients with chronic CHF and a left ventricular ejection fraction <35%. All patients underwent a complete echocardiographic evaluation that systematically included the measurement of the tricuspid annular plane systolic excursion (TAPSE). During a follow-up period of 24 +/- 14 months, 45 patients died and 7 underwent emergency heart transplantation. At the multivariate survival analysis (Cox regression model) backward stepwise selection identified a prognostic model with 2 parameters: New York Heart Association (NYHA) class III or IV and TAPSE < or =14 mm (p <000). In a subgroup of 97 patients in sinus rhythm in whom mitral inflow Doppler variables could be measured, survival was further analyzed according to a model in which the significant parameters were included in the same order as usually used in routine clinical practice: clinical variables first, left ventricular function data second, mitral Doppler variables third, and indexes of right ventricular (RV) function last. TAPSE < or =14 mm added significant (p <0.03) prognostic information to NYHA class III or IV, left ventricular ejection fraction of <20%, and mitral deceleration time of < 125 ms. In conclusion, in patients with CHF, TAPSE adds significant prognostic information to the NYHA clinical classification, to the echocardiographic evaluation of left ventricular function, and to mitral Doppler variables. Furthermore, the measurement of TAPSE is easy to obtain in all patients, irrespective of heart rate and rhythm.

The effects of iloprost infusion on microcirculation is independent of nitric oxide metabolites and endothelin-1 in chronic peripheral ischaemia.

BACKGROUND: Endothelial vascular tone modulators are thought to be involved in aetiopathogenesis of systemic sclerosis (SS) and of peripheral artery occlusive disease (PAOD). Iloprost, a prostacyclin (PGI2) analogue, induces clinical benefit in patients suffering from peripheral ischaemia. This study was performed to investigate the effect of this drug on endothelial function in vivo to elucidate the role of vascular tone modulators. METHODS: Fourteen PAOD and 15 SS patients were treated for 24 and 10 days respectively. On the first day, before and after therapy, nitric oxide metabolites (NO2-/NO3-) and endothelin-1 (ET-1) plasma concentrations were detected; moreover, the endothelium-dependent vasodilatation in response to artificial ischaemia was evaluated by means of an echo-Doppler device. RESULTS: The echo-Doppler evaluation showed that the percentage of arterial reactive dilatation was not modified by placebo or by iloprost, and that the increase in blood velocity flow lasted for a significant longer time after drug infusion (226.79 +/- 17.49 vs. 310.71 +/- 36.32 s; P > 0.04). NO2-/NO3- and ET-1 plasma concentration were higher in patients than in control subjects (P < 0.004). After 6 h of iloprost infusion, no significant modifications were detected. CONCLUSION: This study provides evidence that iloprost enhances the microvascular functional capacity and clinical benefit for patients. The effects of the drug seem to be independently or not directly correlated with its interactions with vascular tone modulators such as NO2-/NO3- or ET-1.

Towards the physical map of the Trypanosoma cruzi nuclear genome: construction of YAC and BAC libraries of the reference clone T. cruzi CL-Brener

Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome have to capitalize on three main advantage of the parasite genome, namely (a) its small size, (b) the fact that all chromosomes can be defined, and many of them can be isolated by pulse field gel electrophoresis, and (c) the fact that simple Southern blots of electrophoretic karyotypes can be used to map sequence tagged sites and expressed sequence tags to chromosomal bands. A major drawback to cope with is the complexity of T. cruzi genetics, that hinders the construction of a comprehensive genetic map. As a first step towards physical mapping, we report the construction and partial characterization of a T. cruzi CL-Brener genomic library in yeast artificial chromosomes (YACs) that consists of 2.770 individual YACs with a mean insert size of 365 kb encompassing around 10 genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs) have been constructed, BACI and BACII. Both libraries represent about three genome equivalents. A third BAC library (BAC III) is being constructed. YACs and BACs are invaluable tools for physical mapping. More generally, they have to be considered as a common resource for research in Chagas disease.