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D Alvarez

Publications and source records attributed to D Alvarez.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cytokine therapeutics for asthma: an appraisal of current evidence and future prospects.

Although current pharmacopoeia is effective in alleviating asthma symptomatology, it is equally unable to modify the fundamental immunological basis of the allergic diathesis. The explosion in knowledge of the immunobiology of cytokines that has occurred in the last decade has remarkably clarified our understanding of the pathogenesis of allergic asthma, and has unleashed a plethora of compelling opportunities. In the first part of this review, we will summarize current knowledge on the pathogenesis of allergic asthma, with particular emphasis on relevant cytokine networks. This will position us to appraise critically initiatives in the search to modulate cytokine targets that are key to the expression of the allergic asthma phenotype. We will review the use of recombinant cytokines, soluble cytokine receptors, cytokine receptor antagonists and cytokine inhibitors, in pre-clinical and clinical development. Finally, we will assess the applicability of transgene-based modalities, including anti-sense oligonucleotide technology and gene therapy, as novel therapeutic strategies in the treatment of allergic asthma.

Animals↗
PubMed2001

Lack of adequate attention to elevated blood pressure in an urban hypertensive population.

BACKGROUND: Efforts directed at improving blood pressure (BP) control and outcomes of hypertension require insight into how physicians diagnose and manage hypertension in various practice settings, especially in the non-continuity setting. METHODS: Retrospective, cross-sectional study. Chart review of records of hypertensive patients, and patients with elevated BP, who visited the Urgent Care Center (UCC) of an urban teaching hospital. We examined patients' characteristics associated with the diagnosis and treatment of hypertension. RESULTS: Complaint of hypertension, request for medication refill, history of hypertension and high stages of hypertension, were associated with attention to BP. Complaint of hypertension and request for medication refill were associated with prescription for antihypertensive medications. Eighty percent of stage I, 50% of stage II, and 30% of stage III levels of BP did not have their BP addressed. Attention to the blood pressure reading was significantly associated with referral for follow-up care. CONCLUSIONS: Providers do not adequately acknowledge elevated BP in the UCC. Progress in the fight against hypertension will require a change in the practice of hypertension care in the non-continuity setting to recognize elevated blood pressures during patient encounters.

Adult↗
PubMed2000

Genetic relationships and spatial genetic structure among clonal stocks of Trypanosoma cruzi in Colombia.

Genetic variability in the protozoan causative agent of Chagas' disease, Trypanosoma cruzi, has been analysed in some Latin American countries; Brazil, Bolivia, Chile and Paraguay. Although Colombia is a country displaying enormous biological diversity, few studies have been conducted from the perspective of the population genetics of Trypanosoma cruzi. This study was carried out using 23 Colombian stocks of this protozoan, analysed for 13 isoenzyme loci. The main population genetic results were: (1) Colombia is one of the distribution areas where T. cruzi appears to have the highest genetic variability and heterogeneity in Latin America; (2) the Pgm locus was found in fixed heterozygosis, supporting the presence of diploidy in this organism; (3) the absence of segregating genotypes and the absence of Hardy-Weinberg equilibrium support the view of the existence of a clonal structure as claimed by Tibayrenc and Ayala. Nevertheless, one characteristic of clonal structure, that of over-representation of some identical zymodemes in vast areas of varying environmental conditions, was not found in Colombia. In this country, a strong spatial autocorrelation, with a classic structure of regional patches, was observed.

Animals↗
PubMed2000

Capsular polysaccharide is a major complement resistance factor in lipopolysaccharide O side chain-deficient Klebsiella pneumoniae clinical isolates.

We have previously demonstrated the existence of Klebsiella pneumoniae clinical isolates deficient in the lipopolysaccharide O side chain, the major factor for resistance to complement-mediated killing in this bacterial species. These isolates are complement resistant, and their mechanisms to resist complement were investigated by selecting transposon-generated complement-sensitive mutants. One mutant with a drastically reduced capacity to grow in nonimmune human serum carried the transposon inserted in an open reading frame of a gene cluster involved in capsule synthesis. This mutant produced less capsule, bound more molecules of the complement component C3, and was more sensitive to complement-mediated and opsonophagocytic killings than was the parent strain. Four additional clinical isolates representing four different K serotypes were studied, and results showed that capsular polysaccharide is a major complement resistance factor in these O side chain-deficient isolates.

Bacterial Capsules↗
PubMed2000

Genetic microstructure in two Spanish cat populations. I: genic diversity, gene flow and selection.

The genetic microstructure of two Spanish cat populations (in Barcelona and Alicante) was studied. These populations were in Hardy-Weinberg equilibrium at the locus O . There was significant genetic heterogeneity for most of the loci studied at the colony level, especially, and the subpopulation level in Barcelona, and at the subpopulation level in Alicante, although the amount of heterogeneity was relatively small compared with that found in other mammal species. Therefore, the major part of the gene diversity found was at the level of the small population structure (colonies). This agrees quite well with high theoretical gene flow estimates. The Lewontin-Krakauer test showed, in some cases, significant F tests, which appears to indicate the presence of several selective events on some of the loci studied (diversifying and/or unifying), although some other causes, such as differential gene flow, some different historical and demographic parameters at the time of the introduction of the different alleles within the cities studied, as well as different mutation rates of the loci analyzed, could produce significant Lewontin-Krakauer test values, as well.

Alleles↗
PubMed2000

[Epworth drowsiness scale value in obstructive sleep apnea syndrome].

Hypersomnia is one of the most consulted symptoms among patients evaluated at sleep disorder centers and it is frequently related to obstructive sleep apnea syndrome (OSAS). Our hypothesis is that Epworth sleepiness scale (ESS) is the parameter with the greatest predictive value in the OSAS diagnosis. We compared patients with OSAS diagnosis to a control group. In both groups we compared ESS with body mass index (BMI), neck circumference (NC), waist perimeter (WP). Anthropometric index (BMI, NC and WC), were similar in both groups (p < 0.10). When we analyzed ESS, a score greater than 10 was observed in the OSAS group, with a significant difference between groups (p < 0.001). Epworth sleepiness scale yielded 60% of sensibility, 82% of specificity and a positive predictive value of 85%. The negative predictive value was 52%. Confidence index was 70%. The relationship between OSAS and ESS scale was significant (Pearson Chi-Square value 7.5). Odds Ratio for apneas was 15 and its confidence interval was lower than 1.5 and upper than 141. We conclude that with ESS score exceeding 10 points OSAS should be suspected.

Adult↗
PubMed1999

Von Willebrand factor could be an index of endothelial dysfunction in patients with cirrhosis: relationship to degree of liver failure and nitric oxide levels.

BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between plasma levels of von Willebrand factor (vWF), a marker of endothelial cell activation, and nitric oxide, a powerful vasodilator synthesized by endothelial cells, in 27 patients with cirrhosis at different stages of the disease. These results were compared with those of age-matched normal, healthy subjects (n=10). METHODS: vWF:antigen was measured by electro-immunodiffusion test and serum nitrite and nitrate levels, the stable end products of nitric oxide metabolism, were determined by an enzymatic procedure. RESULTS: vWF:antigen and nitrite/nitrate levels were significantly higher in cirrhotic patients (367+/-185% and 29.3+/-10.8 micromol/l) than in healthy subjects (92+/-20% and 19.2+/-8.3 micromol/l, p<0.05, respectively). Higher levels of vWF:antigen and nitrites/nitrates were observed in patients with more advanced degrees of liver failure, as reflected by quantitative Child-Pugh's score (516+/-154% and 38.3+/-7.8 micromol/l in Child-Pugh > or = 9 vs 227+/-61% and 21.0+/-6.1 micromol/l in Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors were higher in patients with ascites than those without ascites (543+/-158% and 37.8+/-8.9 micromol/l vs 262+/-103% and 24.4+/-8.8 micromol/l, p<0.001, respectively). In the overall series, a highly significant linear correlation between nitrites/nitrates and vWF:antigen levels was observed in patients with cirrhosis (r=0.79, p<0.001). CONCLUSIONS: These results support a cirrhosis-related endothelial dysfunction and suggest that plasma vWF measurement could be useful as a marker of endothelial disturbance in patients with cirrhosis.

Adult↗
PubMed1999

Klebsiella pneumoniae lipopolysaccharide O typing: revision of prototype strains and O-group distribution among clinical isolates from different sources and countries.

We have previously described an inhibition enzyme-linked immunosorbent assay method for the O typing of O1 lipopolysaccharide from Klebsiella pneumoniae which overcomes the technical problems and limitations of the classical O-typing method. In this study, we have extended the method to all of the currently recognized O types. The method was validated by studying the prototype strains that have defined the O groups by the classical tube agglutinatination O-typing method. Based on these results, we confirmed the O types of 60 of 64 typeable strains, and we propose a revised O-antigenic scheme, with minor but necessary changes, consisting of serogroups or serotypes O1, O2, O2ac, O3, O4, O5, O7, O8, and O12. Application of this typing method to 638 K. pneumoniae clinical isolates from Denmark, Spain, and the United States from different sources (blood, urine, and others) showed that up to 80% of these isolates belong to serotypes or serogroups O1, O2, O3, and O5, independently of the source of isolation, and that a major group of nontypeable isolates, representing about 17% of the total, consists of half O+ and half O- strains. Differences were observed, however, in the prevalence of the lipopolysaccharide O types or groups, depending on the country and isolation source.

Denmark↗
PubMed1999

Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice.

The objective of this study was to investigate the effect of airway gene transfer of interleukin (IL)-10, a cytokine with potent anti-inflammatory and immunoregulatory activities, on allergic mucosal sensitization. We used a recently described murine model that involves repeated exposures to aerosolized ovalbumin (OVA), daily for 10 d, in the context of granulocyte macrophage colony-stimulating factor (GM-CSF) expression in the airway environment achieved by intranasal delivery of a replication-deficient adenovirus carrying the GM-CSF transgene. The resulting inflammatory response was characterized by a T-helper 2 cytokine profile and marked airway eosinophilia. After complete resolution of the inflammatory response (Day 28), a single exposure to OVA reconstituted airway eosinophilia and induced airway hyperresponsiveness. We show that concurrent expression of IL-10 inhibited GM-CSF-driven OVA-specific inflammation in a dose-dependent manner. Specifically, IL-10 decreased the number of mononuclear cells, neutrophils, and eosinophils in the bronchoalveolar lavage fluid (BALF). Histologic evaluation of the tissue corroborated the findings in the BALF. Concurrent expression of IL-10 at the time of mucosal sensitization abrogated both the cellular and physiologic recall responses in vivo. Studies in interferon (IFN)-gamma knockout mice demonstrated that prevention of airway eosinophilia by IL-10 was IFN-gamma-independent and that expression of IL-10 was associated with decreased levels of IL-4, IL-5, and tumor necrosis factor-alpha in the BALF. Flow cytometric analysis of dispersed lung cells showed that expression of IL-10 in the airway reduced the absolute number of Class II major histocompatibility complex (MHC)(+)/CD11c(+) (dendritic cells) and Class II MHC(+)/Mac-1(bright) (macrophages) cells expressing the costimulatory molecules B7.1 and B7.2 by 30%. However, IL-10 coexpression did not prevent expansion of CD4 and CD8 T cells or expression of the early activation marker CD69 on T cells. Thus, airway gene transfer of IL-10 altered the immune response to OVA in a way that resulted in inhibition of airway inflammation. These findings suggest that development of an immunoregulatory strategy based on IL-10, alone or in combination with GM-CSF, warrants further consideration.

Adenoviridae↗
PubMed1999

Lymphocyte populations in tuberculous pleural effusions.

Different systemic and local responses to mycobacterial antigens suggest an active compartmentalization of responsive lymphocytes to tubercular antigens. This fact, observed in pleuritic processes, raises doubts about the accuracy of information obtained in the study of cells taken solely from peripheral blood. For this reason we decided to study the concept of compartmentalization in 140 patients suffering from pleural effusions. Patients were classified into six groups according to the aetiology of the effusion: group I, tuberculous, n = 23; group II, paraneoplastic, n = 41; group III, metapneumonic empyematous, n = 5; group IV, transudate, n = 38; group V, miscellaneous exudate, n = 19; group VI, unknown aetiology, n = 14. In each group we studied the lymphocyte population by using flow cytometry with doubly fluorescent monoclonal antibodies: B [expressing human lymphocyte antigen (HLA)-DR on the surface], T (CD3+), CD4+ and CD8+, and the subpopulation of activated T lymphocytes (together expressing CD3 and HLA-DR on the surface) (CD3+DR+). The study of these subpopulations in peripheral blood did not yield valuable results, but the CD3+DR+ population in pleural fluid demonstrated a diagnostic efficiency of 84% [positive predictive value (PPV) 51%, negative predictive value (NPV) 96%] at a cut-off value of 80.4 cells/mm3. The CD3+DR+ pleural fluid/peripheral blood ratio demonstrated an efficiency of 83% (PPV 50%, NPV 96%), and showed a statistically significant difference (P < 0.02) with regard to all the diagnostic groups, with the exception of the paraneoplastic effusions. The lymphocytic subpopulations study confirms the concept of compartmentalization in tuberculous pleuritis, as shown by the greater number of activated T lymphocytes present in pleural fluid in comparison with peripheral blood in tuberculous pleuritis, a 98% efficiency of adenosine deaminase (ADA) determination in pleural fluid versus a 50% value in peripheral blood, predominance of helper cells (CD4+) in pleural fluid and suppressor cells (CD8+) in peripheral blood, a greater CD4+/CD8+ ratio in pleural fluid than in peripheral blood, and a significant correlation of ADA-CD3+DR+ in pleural fluid, which does not occur in peripheral blood.

Adenosine Deaminase↗
PubMed1999

In vitro efficacy of N-duopropenide, a recently developed disinfectant containing quaternary ammonium compounds, against selected gram-positive and gram-negative organisms.

OBJECTIVE: To study the efficacy of N-duopropenide against various gram-positive and gram-negative organisms. SAMPLE POPULATION: One field strain each of Pasteurella multocida subsp multocida, Staphylococcus aureus, Listeria monocytogenes, and L ivanovii, and 2 field strains of Escherichia coli. PROCEDURE: Strains were tested with and without serum as organic matter, using quantitative suspension and carrier tests. Six concentrations of active ingredient (0.005, 0.01, 0.05, 0.11, 0.27, and 0.55%) and 6 contact times (15 and 30 seconds and 1, 3, 5, and 10 minutes) were studied for each. RESULTS: Globally, N-duopropenide was more effective in suspension tests than in carrier tests, and when organisms were suspended in saline solution rather than serum. Under the most disadvantageous conditions (carrier test with serum), a concentration of 0.55% N-duopropenide acting for only 15 seconds was effective in inactivating P multocida subsp multocida and was even more effective against the 2 Listeria species tested. For E coli strains, the same concentration also was effective, but after 10 minutes of contact. On the other hand, N-duopropenide was unable to inactivate the S aureus strain in the carrier test with serum, a concentration of 0.55% for 10 minutes was necessary to inactivate it without organic matter; however, N-duopropenide was highly effective against this organism in the suspension test, even with serum. CONCLUSION: N-duopropenide was highly effective in vitro against 5 of the most commonly encountered organisms in clinical veterinary medicine and, consequently, might be a good choice in control measures against common pathogenic organisms in modern production systems.

Aldehydes↗
PubMed1998

Tuberculous pleurisy: a study of 254 patients.

OBJECTIVES: To determine the age at which tuberculous pleural effusions occur, the radiological and biochemical characteristics of the effusions, the sensitivities of the various diagnostic tests, and the utility of combining clinical, radiological, and analytic data in diagnosis. METHODS: We studied the case histories of 254 patients in whom tuberculous pleural effusions were diagnosed with certainty between January 1, 1989, and June 30, 1997, in a Spanish university hospital in a region with a high incidence of tuberculosis. RESULTS: The mean (+/-SD) age of the patients was 34.1+/-18.1 years, and 62.2% were younger than 35 years. The effusion was on the right side in 55.9% of patients, on the left side in 42.5% of patients, and on both sides in 1.6% of patients. In 81.5% of patients, less than two thirds of the hemithorax was affected. Associated pulmonary lesions were detected in 18.9% of patients, of whom 14.6% exhibited cavitation. In 93.3% of the effusions, more than 50% of leukocytes were lymphocytes, and almost all had the biologic characteristics of exudates (98.8% had high total protein contents, 94.9% had high cholesterol levels, and 82.3% had high lactate dehydrogenase levels). All but 1 effusion (99.6%) had an adenosine deaminase (ADA) concentration higher than 47 U/L, 96.8% (123/127) of the effusions had high ADA2 levels, and 89% (73/82) of the effusions had high interferon gamma levels. Adenosine deaminase 2 contributed 72.2%+/-12.5% (mean +/- SD) of total ADA activity. Total ADA activity was significantly correlated with ADA2 (r = 0.83) and with interferon gamma (r = 0.30) levels. Definitive diagnosis was based on the observation of caseous granulomas in pleural biopsy tissue samples in 79.8% of patients, on the results of biopsy cultures in 11.7% of patients, and on pleural effusion cultures in the remaining 8.5% of patients. Results of the tuberculin skin test were positive in only 66.5% of patients. CONCLUSIONS: In these patients, lymphocyte-rich exudative pleural effusions occurred, on average, at a young age, with no preference for either the right or the left side; normally affected no more than two thirds of the hemithorax; and were generally unaccompanied by pulmonary infiltrates. High ADA concentration was a highly sensitive diagnostic sign and was caused by a rise in ADA2 concentration. The most sensitive criterion based on pleural biopsy was the observation of caseous granulomas, and culture of biopsy material further increased overall sensitivity. Negative skin test results were no guarantee of the effusion being nontuberculous. This, together with the low mean age of the patients and the low frequency of associated pulmonary lesions, suggests that tuberculous pleural effusion is a primary form of tuberculosis in this region.

Adenosine Deaminase↗
PubMed1998

Splanchnic hyperemia after liver transplantation in patients with end-stage liver disease.

Systemic and splanchnic hemodynamic parameters were evaluated in 12 patients with cirrhosis before and 3 and 6 months after liver transplantation. Results were compared with those obtained in 8 healthy subjects. Three months after liver transplantation recipients had an increase in mean arterial pressure (98 +/- 7 v 78 +/- 9 mmHg; P < .05), an insignificant decrease in cardiac index (3. 4 +/- 0.6 v 4.0 +/- 1.0 L . min-1 . m-2), and a marked increase in peripheral vascular resistance (1,563 +/- 308 v 800 +/- 205 dyne . s . cm-5; P < .05) compared with pretransplantation values. Portal blood flow was also significantly increased (1,494 +/- 200 v 829 +/- 130 mL/min; P < .05). These hemodynamic changes were more pronounced 6 months after transplantation (mean arterial pressure, 100 +/- 8 mmHg; cardiac index, 3.0 +/- 1.0 L . min-1 . m-2; P < .01; peripheral vascular resistance, 1,680 +/- 405 dyne . s . cm-5; portal blood flow, 1,520 +/- 180 mL/min). Systemic hemodynamics 6 months after liver transplantation were similar to those observed in the healthy control group (mean arterial pressure, 95 +/- 6 mmHg; cardiac index, 2.9 +/- 0.9 L . min-1 . m-2; peripheral vascular resistance, 1,480 +/- 380 dyne . s . cm-5). However, portal blood flow was still significantly higher than in healthy controls at 6 months (1,520 +/- 180 v 910 +/- 140 mL/min; P < .05). This study shows that systemic hemodynamics are normalized after liver transplantation. However, an increase in portal blood flow occurs and persists for at least 6 months after liver transplantation. Further studies are needed to clarify the cause of the abnormally high portal flows.

Adult↗