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Biomedical subjects

P Domenech

Publications and source records attributed to P Domenech.

At least 19 recordsLinked to original sources
PubMed2005

Effects of dobutamine on right ventricular function and pulmonary circulation in pulmonary hypertension during liver transplantation.

INTRODUCTION: In the setting of orthotopic liver transplantation (OLT), pulmonary hypertension (PH) affects right ventricular (RV) function. When RV failure occurs, reducing RV afterload, optimizing RV preload, and preserving coronary perfusion through maintenance of systemic blood pressure are the primary goals of intraoperative treatment. PATIENTS AND METHODS: To verify the effect of dobutamine on RV function and RV-arterial coupling, we compared a group of 9 cirrhotic patients with mild PH treated with OLT to a group of 20 patients with normal mean pulmonary artery pressure (MPAP). All patients received dobutamine (5-10 microg/kg/min) to maintain a cardiac index (CI) >3 L/min/m(2), during the anhepatic phase. Hemodynamic profile, using a pulmonary artery catheter, was performed before and during dobutamine infusion, studying MPAP, CI, and RV end-diastolic volume index (RVEDVI). RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio were also calculated. RESULTS: RV contractility (Ees and RVSWI) and afterload (Ea) were significantly higher among the PH group. In both groups, all the studied variables improved with dobutamine: RV contractility increased, afterload decreased, and thus Ees/Ea coupling markedly increased. CONCLUSION: Cirrhotic patients with mild PH who were undergoing OLT still have a reserve of RV contractile performance and pulmonary vasodilation.

Cardiotonic Agents↗
PubMed2005

Portopulmonary hypertension and liver transplantation: hemodynamic consequences at reperfusion.

BACKGROUND: The absence of portopulmonary hypertension (PH) upon preoperative evaluation for liver transplantation (OLT) does not exclude the occasional occurrence of an acquired PH while awaiting a graft. We sought to estimate hemodynamic changes and right ventriculoarterial coupling during reperfusion. METHODS: We studied 11 cirrhotic patients diagnosed with mild PH, according to the current classification: mean pulmonary artery pressure (MPAP)-25 to 34 mm Hg. These patients underwent OLT, using the piggyback technique (group PH). None of them had exhibited criteria for PH on preoperative echocardiography. This cohort was compared with 20 consecutive cirrhotic patients with normal MPAP at OLT. We performed a complete hemodynamic profile using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) before and 5 minutes after reperfusion. The variables were MPAP and right ventricular (RV) end-diastolic volume index (RVEDVI). Using standard formulas we calculated RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio. Systolic ventricular function was expressed as RVSWI versus RVEDVI. RESULTS: During the anhepatic phase, MPAP, Ees, Ea, and RVSWI were higher in the PH group; but RVEDVI was lower. After reperfusion the pressure (MPAP), contractility (RVSWI) and preload (RVEDVI) increased in both groups. However, afterload (Ea) decreased in the non-PH group; accordingly, Es/Ea increased only in these patients. DISCUSSION: At reperfusion, the expansion in preload and cardiac output, without a similar afterload decrease, is responsible for the steady increase in pressure. Our results have shown that in the PH patient group, systolic ventricular function improves during reperfusion by a Frank-Starling mechanism; however, ventricular-arterial uncoupling is maintained (Ees/Ea < 1) because ventricular contractility is not appropriately balanced by simultaneous declines in afterload.

Hemodynamics↗
PubMed2005

Differential response of the systemic and pulmonary circulation related to disease severity of cirrhosis.

BACKGROUND: In cirrhotic patients, the degree of hepatic insufficiency has been related to a physiological landmark: arterial vasodilatation. We sought to assess how the severity of disease, which was stratified according to the Child-Pugh criteria, influences the pulmonary and systemic circulation among patients undergoing liver transplantation. METHODS: We studied 86 cirrhotic patients in three groups: grade A (n = 10), grade B (n = 54), and grade C (n = 22). The outurnes were classified based upon a complete hemodynamic profile obtained using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) after induction of anesthesia. The variables were mean arterial and pulmonary artery pressures and cardiac index (CI). Using standard formulae, afterload was calculated as elastance of systemic (Es) and pulmonary (Ep) arterial beds, expressed by the ratio of end-systolic pressure to stroke volume. The relation between pulmonary and systemic circulation was also evaluated by the ratio (Ep/Es). RESULTS: Es was significantly lower in each class than in previous one. Also, Ep was smaller in class B than in class C patients. In addition, CI was significantly higher with disease severity. CONCLUSION: We observed that the hyperdynamic circulation in cirrhosis is directly related to severity of disease. Nevertheless Ep/Es was progressively higher among each group; these data suggest that the hyperdynamic circulation is mainly due to circulatory alterations in the splanchnic area. We conclude that pulmonary vasodilatation is directly related to the severity of cirrhosis, although its evolution is independent of other vascular areas.

Blood Circulation↗
PubMed2004

[Use of teleradiology in the evaluation and management of head-injured patients. Results of a pilot study of a link between a district general hospital and a neurosurgical referral center].

UNLABELLED: Because of the centralization of neurosurgical services, many head-injured patients who are initially evaluated in district general hospitals need to be transferred to a high technology centre for neurosurgical assessment. However, after assessment, many of these patients are sent back to the original hospital. Establishing a teleradiological system between the two hospitals would eliminate these unnecessary transfers. OBJECTIVES: 1) to describe our initial experience and the results of a pilot study of the teleradiological link between a district general hospital and a tertiary hospital for neurosurgical assessment of head-injured patients, 2) to describe the infrastructure and the technological support required for this project, 3) to analyse the effects of the teleradiological link in both centers (referring and receiving), 4) to evaluate the effectiveness of the system in avoiding unnecessary transfers, and 5) to assess its effectiveness in improving the speed and the quality of transfers in head-injured patients. MATERIAL AND METHODS: In January 1998, the Neurotraumatology Unit of Vall d'Hebron University Hospital established a teleradiological link with the General Hospital of Vic for the neurosurgical evaluation of headinjured patients. The General Hospital of Vic sent the patients' clinical information by fax. CT scan images were digitalized, compressed and prepared for transmission with the StatView program, and were then transmitted by modem to the receiving center. The duty neurosurgeon viewed the images on a PC screen using MutiView software. After evaluating this clinical and radiological information the neurosurgeon sent a report back to the referring center recommending transfer or management (admission, observation, etc.). RESULTS: We analyse the results of our experience 5 years after the implantation of the teleradiological link. CONCLUSIONS: The use of teleradiology in the daily management of head-injured patients provides clear benefits and leads to a more rational use of resources, thus significantly reduces costs. The effectiveness of the system in reducing the interval between the injury and treatment in severe cases depends more on the infrastructure of the health system in each geographical area than on sophisticated telemedicine systems. These methods should be accompanied by other measures designed to hasten the transfer of selected patients.

Adolescent↗
PubMed2002

Inactivation of the Mycobacterium tuberculosis Nramp orthologue (mntH) does not affect virulence in a mouse model of tuberculosis.

Mycobacterium tuberculosis is an intracellular pathogen which can survive and multiply within the phagosomal compartment of the macrophage, and in doing so has to withstand the various macrophage defense mechanisms, which include limitation of iron and other metals. Analysis of the complete genome sequence of M. tuberculosis revealed an extensive array of cation transporters, including mntH, an orthologue of the eukaryotic Nramp (natural resistance-associated macrophage protein) gene, that encodes a proton-dependent divalent metal transporter. To assess the effect of this transporter on intracellular survival and pathogenesis, an mntH knock-out mutant of M. tuberculosis H37Rv was created and assayed in bone marrow-derived macrophages and in a murine model of tuberculosis. In neither of these systems was any loss of fitness associated with inactivation of mntH, demonstrating that Nramp orthologues are not important determinants of mycobacterial virulence.

Animals↗
PubMed2001

Role of OxyS of Mycobacterium tuberculosis in oxidative stress: overexpression confers increased sensitivity to organic hydroperoxides.

Mycobacterial genomics has uncovered a novel regulatory gene, oxyS, belonging to the LysR family. There is extensive similarity in the DNA-binding domain of OxyS with that of OxyR, the oxidative stress response protein of many bacteria. Since the oxyR gene of Mycobacterium tuberculosis has been multiply inactivated during evolution it was conceivable that some of its functions could be effected by OxyS. It is shown here that OxyS is produced at low levels and that there are at least three different oxyS alleles present in clinical isolates of M. tuberculosis that are susceptible or resistant to isoniazid. Overproduction or depletion of OxyS did not affect susceptibility to isoniazid but increasing the concentration of the regulator lowered levels of the alkyl hydroperoxide reductase, AhpC, and rendered the tubercle bacillus more susceptible to organic hydroperoxides.

Amino Acid Sequence↗
PubMed2001

Mycobacterium tuberculosis in the post-genomic age.

Since the publication of the complete genome sequence of Mycobacterium tuberculosis in 1998, there has been a marked intensification and diversification of activities in the field of tuberculosis research. Among the areas that have advanced spectacularly are comparative genomics, functional genomics-notably the study of the transcriptome and proteome - and cell envelope biogenesis, especially as it relates to the mechanism of action of antimycobacterial drugs.

Antigenic Variation↗
PubMed2001

Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis.

Mycobacterium tuberculosis has two genes for ferric uptake regulator orthologues, one of which, furA, is situated immediately upstream of katG encoding catalase-peroxidase, a major virulence factor that also activates the prodrug isoniazid. This association suggested that furA might regulate katG and other genes involved in pathogenesis. Transcript mapping showed katG to be expressed from a strong promoter, with consensus -10 and -35 elements, preceding furA. No promoter activity was demonstrated downstream of the furA start codon, using different gene reporter systems, indicating that furA and katG are co-transcribed from a common regulatory region. The respective roles of these two genes in the isoniazid susceptibility and virulence of M. tuberculosis were assessed by combinatorial complementation of a Delta(furA-katG) strain that is heavily attenuated in a mouse model of tuberculosis. In the absence of furA, katG was upregulated, cells became hypersensitive to isoniazid, and full virulence was restored, indicating that furA regulates the transcription of both genes. When furA alone was introduced into the Delta(furA-katG) mutant, survival in mouse lungs was moderately increased, suggesting that FurA could regulate genes, other than katG, that are involved in pathogenesis. These do not include the oxidative stress genes ahpC and sodA, or those for siderophore production.

Animals↗
PubMed1997

The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study.

Fibrinolysis has been recognized as an important cause of intraoperative bleeding during orthotopic liver transplantation (OLT). Several investigators have used prophylactic administration of aprotinin in patients to inhibit fibrinolysis and to decrease transfusion requirements, morbidity, and mortality. Nevertheless, the role of aprotinin in this situation is not yet clear. The goal of this study was to determine the effects of prophylactic administration of aprotinin on intraoperative bleeding and blood requirements, and on hemostatic changes during OLT. Eighty consecutive patients were included in a double-blind, prospective study and were randomized in two groups. In group A (n = 39), an initial dose of 2 x 10(6) kallikrein inactivator units (KIU) of aprotinin was administered in the induction of anesthesia followed by infusion of 5 x 10(5) KIU/h until the end of the procedure. The control group (n = 41) received an identical volume of saline solution. The majority of the operations were performed with vena cava preservation (piggy-back technique) without venovenous bypass. During the anhepatic phase, a significant increase in levels of tissue plasminogen activator, thrombin-antithrombin complexes (TAT) and D-dimers (DD) was noted in both groups. A significant increment of TAT was observed in group A during reperfusion. The remaining hemostatic parameters were similar in both groups. Intraoperative requirements of packed red cells, fresh-frozen plasma (FFP), platelets, and cryoprecipitate were similar in the two groups. Our results suggest that prophylactic administration of aprotinin is not useful in reducing bleeding and blood product requirements during OLT.

Adolescent↗
PubMed1997

Mycobacterium mageritense sp. nov.

Strains of a new species of rapidly growing, nonphotochromogenic mycobacteria, Mycobacterium mageritense, were isolated from human sputum. The growth characteristics, acid fastness, and mycolic acids of the isolates were consistent with those of Mycobacterium species. The isolates were identified as members of a new species by performing a biochemical analysis and DNA-DNA hybridization experiments, and by comparing the sequences of several conserved genes, such as the 16S rRNA, hsp65, and sodA genes. A phylogenetic analysis in which 16S rRNA and sodA sequences were used identified M. mageritense as a novel distinct species and placed M. mageritense between members of the Mycobacterium fortuitum complex and the thermotolerant rapidly growing group. Our results demonstrate that the taxonomic value of sodA sequence analysis in the genus Mycobacterium is similar to the well-established value of 16S rRNA sequence analysis.

Bacterial Proteins↗
PubMed1997

Effects of overexpression of the alkyl hydroperoxide reductase AhpC on the virulence and isoniazid resistance of Mycobacterium tuberculosis.

Mutations to the regulatory region of the ahpC gene, resulting in overproduction of alkyl hydroperoxide reductase, were encountered frequently in a large collection of isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis but not in INH-susceptible strains. Overexpression of ahpC did not seem to be important for INH resistance, however, as most of these strains were already defective for catalase-peroxidase, KatG, the enzyme required for activation of INH. Transformation of the INH-susceptible reference strain, M. tuberculosis H37Rv, with plasmids bearing the ahpC genes of M. tuberculosis or M. leprae did not result in a significant increase in the MIC. Two highly INH-resistant mutants of H37Rv, BH3 and BH8, were isolated in vitro and shown to produce no or little KatG activity and, in the case of BH3, to overproduce alkyl hydroperoxide reductase as the result of an ahpC regulatory mutation that was also found in some clinical isolates. The virulence of H37Rv, BH3, and BH8 was studied intensively in three mouse models: fully immunocompetent BALB/c and Black 6 mice, BALB/c major histocompatibility complex class II-knockout mice with abnormally low levels of CD4 T cells and athymic mice producing no cellular immune response. The results indicated that M. tuberculosis strains producing catalase-peroxidase were considerably more virulent in immunocompetent mice than the isogenic KatG-deficient mutants but that loss of catalase-peroxidase was less important when immunodeficient mice, unable to produce activated macrophages, were infected. Restoration of virulence was not seen in an INH-resistant M. tuberculosis strain that overexpressed ahpC, and this finding was confirmed by experiments performed with appropriate M. bovis strains in guinea pigs. Thus, in contrast to catalase-peroxidase, alkyl hydroperoxide reductase does not appear to act as a virulence factor in rodent infections or to play a direct role in INH resistance, although it may be important in maintaining peroxide homeostasis of the organism when KatG activity is low or absent.

Animals↗
PubMed1996

Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic patients.

To evaluate whether or not activated coagulation is present in the preclinical phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree relatives of type 2 diabetic patients and 21 matched controls with no family history of diabetes. We determined the plasma levels of prothrombin fragment 1 + 2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight-1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l-1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher in relatives, without significant differences in the other haemostatic variables. Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post-infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no significant differences in insulin sensitivity. Fifteen relatives were glucose-intolerant and had lower beta-cell function and insulin sensitivity than glucose-tolerant relatives. Both subsets of relatives exhibited higher levels of prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree relatives of type 2 diabetic patients present an activated coagulation, even in the absence of minor degrees of glucose intolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabetes.

Adult↗
PubMed1995

Cloning and expression of the Mycobacterium fortuitum superoxide dismutase gene.

In this paper we report the cloning, sequencing and expression of the superoxide dismutase (sod) gene from Mycobacterium fortuitum. A single gene was found to code for superoxide dismutase activity with its identity being confirmed by expression in M. aurum. The amino acid sequence was found to be similar to that of superoxide dismutases of several other origins. A region downstream of the sod gene also showed similarities to the corresponding sequences of the two main mycobacterial pathogens: M. leprae and M. tuberculosis. Analysis of enzymatic activity showed this enzyme in M. fortuitum required manganese as cofactor.

Base Sequence↗
PubMed1995

[Fibrinogen and factor VII in women with dyslipidemia. The preliminary results of the Bellvitge-Costa de Ponent Study. The Bellvitge Study Group].

BACKGROUND: The distribution of serum fibrinogen levels and factor VII in a population of dyslipemic women and their association with other cardiovascular risk factors are herein described. METHODS: Dyslipemic women between 40-70-years of age without cardiovascular disease and with no hypolipemic treatment who attended 21 primary health care consultations were studied. The following data were collected in a questionnaire: smoking habit, high blood pressure, alcohol consumption and menopause. The analytical parameters determined were: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fibrinogen and factor VII. The Pearson correlation coefficient was determined to evaluate the association of fibrinogen and factor VII with other cardiovascular risk factors. RESULTS: Serum fibrinogen levels correlated positively with LDL-cholesterol and with the body mass index and negatively with HDL-cholesterol. Factor VII correlated positively with the triglycerides and total cholesterol. No significant differences were observed in the hematic factors among the hypertensive women and those who were not hypertensive. The same was observed in diabetic and in the pre- and postmenopausal women. CONCLUSIONS: In this transversal study a relationship was found between serum fibrinogen level and factor VII activity and other known cardiovascular risk factors.

Adult↗
PubMed1995

Prevalence of antiphospholipid antibodies in patients with ankylosing spondylitis.

OBJECTIVE: To establish the prevalence of antiphospholipid antibodies (aPL) in a group of patients with ankylosing spondylitis (AS). The relation of the antibodies with different clinical and analytical features was studied. METHODS: Eighty-four patients with AS (71 men) and 40 age and sex matched controls were studied. aPL determinations included: anticardiolipin antibodies (aCL) of the IgM, IgG, and IgA classes, the presence of lupus anticoagulant (LAC), and a false positive serologic test for syphilis. Comparisons between variables were done by Student t test, Mann-Whitney test and Chi squared test. Correlations between aPL and clinical variables were performed by Pearson coefficients. RESULTS: Twenty-four patients with AS (29%) has positive IgG aCL, compared with only 2 cases in the control group (5%) (p < 0.002). There were no differences in other aPL determinations between patients and controls. There was no correlation between the presence of aCL (IgG, IgM, or IgA) and LAC and the different aspects of the disease. Two patients fulfilled the criteria for antiphospholipid syndrome. CONCLUSION: Our results indicate the presence of IgG aCL in patients with AS higher than in the normal population but their relation with thrombosis and other systemic manifestations seems weak.

Adult↗