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Biomedical subjects

M Alvarez-Mon

Publications and source records attributed to M Alvarez-Mon.

At least 19 recordsLinked to original sources
PubMed2005

Different proinflammatory cytokine serum pattern in neonate patients undergoing open heart surgery. Relevance of IL-8.

The purpose of this work was to investigate the clinical significance of serum levels of proinflammatory cytokines in pediatric patients undergoing cardiopulmonary bypass. We divided the patients in two groups: 8 neonates, and 19 non-newborn children. IL-1beta, IL-6, IL-8, and TNF serum levels were quantified before sternotomy, at admission to the PICU (30 min postoperatively), 24 h after the onset of surgery and 3 days after the operation. Surgical cardiac stress elicits significant increments of IL-6, IL-8 and TNF serum concentrations in both neonates and non-neonates, regardless of their preoperative clinical condition. However, in newborns the magnitude of the proinflammatory cytokine increments was, in particular with IL-8, remarkably greater than in older children. Moreover, neonate and non-neonate patients showed clearly disparate patterns of serum concentrations over time of both IL-8 and TNF. There was a marked relationship between IL-8 levels and postoperative morbidity, evaluated by pulmonary dysfunction, days on inotropic support and days of PICU stay in both neonates and non-neonates patients. In contrast, we found no relationship between serum levels of IL-6 and TNF and postoperative clinical data. Newborn and non-newborn patients undergoing cardiopulmonary bypass exhibit dissimilar patterns of proinflammatory cytokines. IL-8 might be implicated in the multiorganic dysfunction related to cardiopulmonary bypass in pediatric patients.

Age Factors↗
PubMed2004

Loss of lineage antigens is a common feature of apoptotic lymphocytes.

The analysis of apoptosis in cell populations involves the detection of their specific lineage antigen (LAg) expression. This experimental approach relies on their assumed constant expression, but it is unclear whether such expression is actually maintained during cell death. We examined whether the loss of LAgs is a common feature of apoptotic lymphocytes and whether some might completely lose their LAgs. The changes in the expression of CD3, CD5, CD8, CD4, CD28, CD56, and CD19 were monitored in highly purified lymphocyte populations obtained by negative selection in a fluorescence-activated cell sorter. These were cultured for 24 h with or without phytohemagglutinin or staurosporin. For each LAg-positive subset studied, apoptosis was consistently more common among cells showing partial or total loss of LAg expression compared with cells maintaining their initial LAg levels. The kinetics of expression loss was rapid for CD8, CD56, and CD28, and more than 80% of initial expression was lost in the early stages of apoptosis but was slower for CD3, CD5, and CD4. For CD3 and CD5, expression was dependent on the apoptotic stimulus used. It is interesting that loss of antigen expression was independent of cell size. This phenomenon was also found in nonmanipulated, highly pure CD19 B lymphocytes of peripheral blood mononuclear cells from B chronic lymphocytic leukemia patients. Loss of LAg expression appeared to be a common feature of apoptotic lymphocytes under all the conditions assayed. The different kinetic patterns of LAg loss suggest apoptotic cells might actively regulate this process.

Antigens, CD↗
PubMed2004

[Effect of immunomodulator AM3 on the exacerbations in patients with chronic bronchitis: a systematic review of controlled trials].

OBJECTIVE: Analyze the effect of AM3, an oral immunomodulator, on the exacerbations and on the use of antibiotics in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic search of controlled clinical trials that used AM3 in some treatment group and that included data on the clinical effects of this drug on patients with COPD. SELECTED VARIABLES: Nine studies were detected in which the clinical effectiveness of AM3 was evaluated in relation to the number of infectious exacerbations, their length, and the length of the antibiotic treatment used. RESULTS: In comparison with placebo group, the average number of excaerbations suffered by the patients treated with AM3 declined significantly in 0.31 units (p < 0.001; 95% confidence interval: 0.20-0.42), without heterogeneity among the different studies (Q = 6.62; p > 0.43). With regard to the average length of the exacerbations and the average length of the antibiotic treatment used for the exacerbations, both variables declined significantly in the group treated with AM3 (3.10 days, p < 0.001, and 8.07 days, p < 0.001, respectively) but this positive effect could not be confirmed because trials were close to heterogeneity. CONCLUSIONS: The results of this systematic review show that AM3 has a clinical effect in the prevention of exacerbations of COPD patients because reduces significantly their number. This could be related to a slowing in the progression of the deterioration in the respiratory function with a potential impact on the quality of life of the patients. Furthermore, these data imply a positive therapeutic result and a possible decline in development of bacterial resistances secondary to the frequent and indiscriminate use of antibiotics in these patients.

Adjuvants, Immunologic↗
PubMed2004

Pulmonary injuries and cytokine levels after the intraperitoneal administration of pancreatic homogenates in rats.

INTRODUCTION: Our objective was to investigate the effects of the administration of pancreatic homogenates, with or without enzymatic activation, to healthy animals regarding cytokine serum levels and the development of pulmonary distress. MATERIAL AND METHODS: 106 male Wistar rats, divided into three groups, were studied: group A, intraperitoneal administration of homogenates activated with enterokinase; group B, homogenates without enterokinase; and group C, control group with administration of physiological saline solution. Each group was divided into 4 subgroups according to the time of sacrifice: 0, 2, 6 and 24 hours. We studied the pulmonary and pancreatic histology, serum parameters of renal and hepatic function, and serum levels of IL-1beta, IL-6 and TNFalpha. RESULTS: There was no mortality in any group. Pancreatic disorders in A and B groups were noted at 24 hours. These two groups had statistically significant higher transaminase serum levels than those of the control group, as well as statistically significant higher creatinine levels in group A. IL-1beta showed a statistically significant higher level at 6 h in both groups, A and B, but was higher in group A, which also exhibited significant pulmonary histologic damage with respect to controls at 6 h. CONCLUSIONS: The higher IL-1beta level in group A may result from production by peritoneal macrophages under the influence of homogenate enzymatic activation. This may be the reason for lung damage.

Animals↗
PubMed2003

[Inflammatory pathology in urology. Standardization].

The recognition, identification and management of the many events taking place in relation to an inflammatory response has become a rapidly growing field in medicine over the last few years. In this sense, the progress made in later years in the study of the molecular and cellular mechanisms of tissue inflammatory reactions in sites such as synovial membranes, gut mucosa, vascular endothelium etc, is considered highly relevant. A number of authors conscious of such events work on the standardization of clinical models of the inflammatory responses of genitourinary organs resulting from the action of a variety of harmful events. This review is warranted by the prevalence and morbidity and mortality of inflammatory conditions, as well as the complex work of incorporating to Urology the findings from other Biomedical Sciences.

Bacterial Infections↗
PubMed2002

Newborn patients exhibit an unusual pattern of interleukin 10 and interferon gamma serum levels in response to cardiac surgery.

OBJECTIVE: The aim of this study was to determine the clinical significance of serum levels of interleukin 10 and interferon gamma in pediatric patients undergoing cardiopulmonary bypass. METHODS: We divided the patients into 2 groups: 8 neonates and 19 non-newborn children. Interleukin 10 and interferon gamma serum levels were quantified before sternotomy, at admission to the pediatric intensive care unit (30 minutes postoperatively), 24 hours after the onset of the operation, and 3 days after the operation. RESULTS: Newborn patients displayed significantly greater amounts of serum interleukin 10 than older children, not only in regard to the peak level achieved but also at every postoperative time point analyzed. In contrast, no significant changes in interferon gamma serum levels were observed in neonates at any time point, whereas non-newborn pediatric patients showed a significant increase in interferon gamma serum concentrations immediately after the operation. This unusual pattern of cytokine response in newborn patients was not associated with modifications in cortisol serum levels. Furthermore, although neonates had significantly different surgical and clinical variables than did the non-newborn pediatric patients, the variation in interleukin 10 production in neonates could not be accounted for by differences in the magnitude of surgical injury. In the group of neonates, there were significant positive correlations between peak interleukin 10 serum levels and both partial pressure of arterial oxygen/fraction of inspired oxygen ratio and postoperative body weight gain. CONCLUSIONS: Newborn patients undergoing cardiopulmonary bypass exhibit a distinctive biologic response pattern characterized by high levels of serum interleukin 10 without changes in serum interferon gamma. This cytokine imbalance could have potential clinical implications.

Cardiac Surgical Procedures↗
PubMed2002

Lung changes and cytokine levels in a model of experimental acute pancreatitis.

AIM: Prognosis of acute pancreatitis is related mainly to systemic involvement. The establishment of this systemic inflammation is mediated by proinflammatory cytokines. Our aim is to study serum levels of some proinflammatory cytokines and the associated damage of the lung in a model of experimental acute pancreatitis. EXPERIMENTAL DESIGN: Eighty seven male Wistar rats were divided into two groups: group A (control) with saline solution administration; group B with acute pancreatitis induced by intraperitoneal caerulein (50 mg/kg every hour, 4 doses). The animals were killed at 0, 2, 6 and 24 hours of the last dose of caerulein or saline solution. Pancreatic and pulmonary histology were examined, and serum levels of IL-1 beta, TNF-alpha and IL-6 were evaluated, as well as some laboratory parameters as indicators of systemic involvement. RESULTS: The administration of caerulein induced an acute edematous pancreatitis without mortality and with a trend towards resolution in 24 hours. IL-1 beta in animals with acute pancreatitis showed significantly higher levels than in the control group at 6 hours. Serum transaminases, urea and creatinine were also significantly higher at 2 and 6 h. The group with acute pancreatitis showed histological lung damage all over the study. CONCLUSIONS: In our model of acute pancreatitis we observed systemic involvement as judged by alterations of serum transaminases and parameters of renal function, as well as histological lung damage, that correlated with an increase in serum levels of IL-1b.

Acute Disease↗
PubMed2001

Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis.

CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance.

Arthritis, Rheumatoid↗
PubMed2001

Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

Adjuvants, Immunologic↗
PubMed2000

Liposomal amphotericin B and amphotericin B-deoxycholate show different immunoregulatory effects on human peripheral blood mononuclear cells.

Conventional preparations of amphotericin B (AmB) at established therapeutic doses are known to increase nonspecific immune responses. It remains to be established whether higher doses of the less toxic liposomal preparation of AmB maintains a beneficial effect on the immune response to fungal infections. Examination of the effect of treatment of human peripheral blood mononuclear cells from healthy subjects with various doses of both liposomal AmB (L-AmB) and deoxycholate AmB (d-AmB) on proliferation, cell viability, and percentage of apoptosis demonstrated that, although both L-AmB and d-AmB at low doses significantly increased nonspecific proliferative responses, L-AmB, but not d-AmB, treatment maintained this beneficial effect at higher doses. High doses of d-AmB, but not L-AmB, resulted in significantly decreased cell viability and increased apoptosis. This study provides further evidence in healthy human subjects for choosing L-AmB over conventional preparations in the clinical treatment of fungal infections requiring systemic high-dose treatment with AmB.

Adjuvants, Immunologic↗
PubMed2000

A new method for the simultaneous analysis of growth and death of immunophenotypically defined cells in culture.

BACKGROUND: Internal standards have been used in flow cytometry methods to enumerate lymphoid subsets and hemopoietic progenitor cells ex vivo. However, the currently available methods cannot be readily applied to the analysis of cultured cells because of the frequent occurrence of cell death during in vitro assays. METHODS: This paper reports a new method for the enumeration of both viable and nonviable cells in culture. Cells were counted with the aid of an internal reference standard of microbeads, and live versus dead cell discrimination was performed using 7-amino-actinomycin D which allows the double staining of surface antigens. RESULTS: The method is more precise, accurate and sensitive than either conventional light microscopy-based or automated cell counting. Additionally, it may be used to accurately measure the number of apoptotic cells in a culture. RESULTS: Through the enumeration of surviving cells it is demonstrated that, when applied to the study of mitogen-activated T lymphocytes, current flow cytometry techniques (which do not use internal standards) for the study of the viability and apoptosis overestimate the fraction of viable cells and underestimate both the fraction of dead and apoptotic cells. CONCLUSIONS: The new method overcomes these limitations and is of use in the in vitro study of cell growth and apoptosis.

Apoptosis↗
PubMed2000

Cost-effectiveness analysis of interferon as adjuvant therapy in high-risk melanoma patients in Spain.

In the randomised clinical trial E1684, the administration of interferon (IFN) alpha-2b resulted in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection. However, and considering the cost and toxicity of IFN, the convenience of its widespread use should be evaluated. The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group. A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years, according to the clinical outcome of the E1684 study. The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient's lifetime. The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model. The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome. In conclusion, in high-risk melanoma patients following surgical resection, the cost-effectiveness of IFN alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month, followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System.

Antineoplastic Agents↗
PubMed2000

HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy.

Hepatitis C virus (HCV) has been proposed as a possible causative agent of chronic thrombocytopenia. We investigated HCV infection in a series of 51 unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and HCV viraemia were detected in 13/51 (22.5%) of cases; this prevalence was particularly significant when compared with HCV seropositivity in age-matched controls (0.4%). Anti-HCV-positive patients, four men and nine women with a median age of 59.3 years (range 36-72), had a mean platelet count of 55.8 x 109/l (range 12-96). Only one of our HCV-positive thrombocytopenic patients had hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non-autoimmune mediated. In six patients, a trial of recombinant alpha2b-interferon (IFN-alpha) given at a dose of 3 MU three times per week for 6-24 months gave a durable (> 1 year) and significant increase in platelet count in all six patients. The maximum increase occurred after 6 months of IFN-alpha therapy. In conclusion, the ability of IFN-alpha to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.

Adolescent↗
PubMed1999

Multivalent structure of an alphabetaT cell receptor.

Whether there is one or multiple alphabetaT cell antigen receptor (TCR) recognition modules in a given TCR/CD3 complex is a long-standing controversy in immunology. We show that T cells from transgenic mice that coexpress comparable amounts of two distinct TCRbeta chains incorporate at least two alphabetaTCRs in a single TCR/CD3 complex. Evidence for bispecific alphabetaTCRs was obtained by immunoprecipitation and immunoblotting and confirmed on the surface of living cells both by fluorescence resonance energy transfer and comodulation assays by using antibodies specific for TCRbeta-variable regions. Such (alphabeta)2TCR/CD3 or higher-order complexes were evident in T cells studied either ex vivo or after expansion in vitro. T cell activation is thought by many, but not all, to require TCR cross-linking by its antigen/major histocompatibility complex ligand. The implications of a multivalent (alphabeta)2TCR/CD3 complex stoichiometry for the ordered docking of specific antigen/major histocompatibility complex, CD4, or CD8 coreceptors and additional TCRs are discussed.

Animals↗
PubMed1999

Impaired mitogenic response of peripheral blood T cells in ulcerative colitis is not due to apoptosis.

An abnormal immune response may play a pathogenic role in ulcerative colitis (UC). Animal models suggest that T-cell regulation may be of central importance in the inflammatory process. Our aims were the characterization of the phenotype and functional status of circulating T-cells in ulcerative colitis patients and to determine if activation-induced cell death in CD4 and CD8 lymphocytes in patients differs from healthy controls. Forty-eight patients (24 women and 24 men) fulfilling the histopathological, clinical, and immunological criteria for UC were studied. T-cell phenotype and function were studied in blood lymphocytes from patients with ulcerative colitis and healthy donors by flow cytometric analysis, as well as [3H]thymidine incorporation. There were no significant differences in the percentage of T-cell subpopulations (CD3, CD4, CD8) and NK cells in the different groups. The percentage of cells in growth phase S+G2M at two and three days of phytohemagglutinin (PHA) stimulation was significantly decreased in UC patients, but the percentage of CD4+ and CD8+ cells in UC patients that showed apoptosis was not significantly different than that in the control group. Proliferative responses to IL-4 also suggested that a reduced responsiveness to this cytokine may be involved in UC. In conclusion, the impaired proliferative response to PHA of T lymphocytes from UC patients is not associated with an in vitro increase in the apoptotic response in CD4+ or CD8+ cells. A reduced IL-4 response may be involved in this peculiar mitogenic response. These changes may be pathogenic or a favorable adaptive mechanism.

Adult↗
PubMed1999

The association between CD2+ peripheral blood lymphocyte subsets and the relapse of bladder cancer in prophylactically BCG-treated patients.

We investigated the potential existence of differences in the distribution of T-lymphocyte subsets and in the proliferative response of these CD2+ cells to polyclonal mitogens in patients with transitional cell bladder carcinoma (SBTCC) treated with prophylactic intracavitary instillations of bacillus Calmette-Guerin (BCG) according to their clinical response to this treatment. Before BCG treatment, different subset distribution (CD8+ and CD3+ CD56+), activation antigen expression (CD3+ HLA- DR+) and proliferative response to mitogenic signals were found in CD2+ cells from SBTCC patients prophylactically treated with BCG who remained free of disease or those who had recurrence of tumour. Otherwise, the prophylactic intracavitary BCG instillations in SBTCC patients are associated with a transitory variation of T-lymphocyte subset distribution (CD4 and CD8) and activation antigens expression (CD25).

Adjuvants, Immunologic↗