Search PubMed⌕ Search

Biomedical subjects

F Arnalich

Publications and source records attributed to F Arnalich.

At least 19 recordsLinked to original sources
PubMed2002

Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis.

This study aims to determine the influence of the polymorphism within the intron 2 of the interleukin-1 receptor antagonist gene (IL-1RN*) on the outcome of severe sepsis, and to assess its functional significance by correlating this polymorphism with the total production of interleukin-1 receptor antagonist (IL-1Ra) protein determined in stimulated peripheral blood mononuclear cells (PBMC). A group of 78 patients with severe sepsis (51 survivors and 27 nonsurvivors) was compared with a healthy control group of 130 blood donors, and 56 patients with uncomplicated pneumonia. We found a significant association between IL-1RN* polymorphism and survival. Thus, after adjusting for age and APACHE II score, multiple logistic regression analysis showed that patients homozygotes for the allele *2 had a 6.47-fold increased risk of death (95% CI 1.01--41.47, P = 0.04). Besides, compared with patients homozygous or heterozygous for the allele *1, IL-1RN*2 homozygotes produced significantly lower levels of IL-1Ra from their PBMC. Our results suggest that insufficient production of this cytokine might contribute, among other factors, to the higher mortality rate found in severe sepsis patients with the IL-1RN*2 homozygous genotype.

APACHE↗
PubMed2001

Intracellular glutathione deficiency is associated with enhanced nuclear factor-kappaB activation in older non-insulin dependent diabetic patients.

Diabetes mellitus may be associated with intracellular glutathione (GSH) deficiency. Since in vivo studies have shown that plasma intracellular GSH plays a key role in regulating the activation of nuclear factor kappaB (NF-kappaB), we have investigated the relationship between intracellular thiols (GSH, homocysteine, cysteine and cysteinyglycine) and NF-kappaB activity in the peripheral blood mononuclear cells (PBMC) of 63 elderly non-insulin dependent diabetes mellitus (NIDDM) patients (28 microalbuminurics and 35 normoalbuminurics) and 30 healthy age- and sex-matched subjects. In addition, we have measured plasma concentrations of these thiol compounds, serum concentrations of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (sVCAM-1), that are partly dependent on the NF-kappaB activation, as well as the serum levels of thiobarbituric acid reacting substances (TBARS), as index of lipid peroxidation. Diabetic patients with microalbuminuria (MAB) and normoalbuminuria had NF-kappaB activity 2.1- and 1.5-fold greater, respectively, than the control group. As compared to normoalbuminuric patients, patients with MAB had significantly higher levels of glycemia, plasma homocysteine, and serum concentrations of TBARS, IL-6 and sVCAM-1 (in all cases, p < 0.01), and significantly lower GSH content in the PBMC (p < 0.05). The intracellular GSH in PBMC correlated with NF-kappaB activation (r = -0.82; p < 0.0001), serum TBARS (r = -0.60; p < 0.001), and with fasting glycemia (r = -0.56; p < 0.001) in patients with MAB, whereas a weaker association between GSH levels in PBMC and NF-kappaB activation (r = -0.504, p < 0.001) was seen in patients without MAB. These results suggest that the decrease of intracellular GSH content in elderly NIDDM patients with MAB is strongly associated with enhanced NF-kappaB activation, which could contribute to the development of increased glomerular capillary permeability and its rapid progression.

Age Factors↗
PubMed2001

Fever of unknown origin: classic and associated with human immunodeficiency virus infection. a comparative study.

Fever of unknown origin (FUO) associated with HIV infection is different from classic FUO. Relevant etiologies, procedures and time to diagnosis were analyzed. Patients admitted with FUO from 1991 to 1996 were prospectively followed. Thirty with classic FUO (group I) and 46 with FUO and HIV (group II) were included. Data on diagnosis, time to achieve it, and procedures were registered. Diagnosis was obtained in 87% and 93% of cases in groups I and II. Infections were the most frequent cause in group II. Collagen diseases were found in group I and absent in group II. Prevalence of neoplasia was similar. Mean time to diagnosis was near 5 weeks. In HIV the predominant diagnostic method was the Lowenstein culture. Invasive methods were similarly employed. It is concluded that predominance of Mycobacteria and absence of collagen diseases make FUO associated with HIV a different form of FUO. No differences were found in approach and time to diagnosis.

Adult↗
PubMed2000

Changes in the intracellular homocysteine and glutathione content associated with aging.

Since moderate hyperhomocysteinemia is an independent risk factor for vascular disease by mean of its oxidant effect and glutathione plays a main role as intracellular redox-regulating agent, we have studied for the first time the total intracellular content of homocysteine in aging. Plasma homocysteine concentration, total intracellular and plasma glutathione, and other related thiol compounds such as cysteine and the glutathione catabolite cysteinglycine were also studied. Forty three healthy elderly subjects and twenty seven healthy young ones were studied. The total intracellular peripheral blood mononuclear cell content was higher for homocysteine, cysteine and cysteinglycine, whereas that of the total glutathione was greatly decreased in elderly people with respect to young ones. Elderly subjects showed significantly higher levels than young ones of total plasma homocysteine and cysteinglycine, but not cysteine, whereas total plasma glutathione levels were increased. In addition, elderly subjects showed significantly decreased plasma vitamin E levels and increased concentrations of serum lipid peroxides measured as TBARS (reaction product of malondialdehyde with thiobarbituric acid). The intracellular glutathione content presented significantly negative correlation with serum TBARS, and intracellular and plasma homocysteine levels. These findings show an increase of homocysteine synthesis associated with aging, which in turn can produce an augmented oxidant effect on endothelium, and an impaired intracellular antioxidant capacity leading to an enhanced lipid peroxidation and decreased total intracellular glutathione content.

Aged↗
PubMed2000

Enhanced acute-phase response and oxidative stress in older adults with type II diabetes.

OBJECTIVE: To test whether oxidative stress could promote a systemic acute-phase response in elderly patients with type II diabetes. DESIGN AND METHODS: In a group of 30 older diabetic patients with poor glycemic control, serum levels of lipid peroxides, measured as thiobarbituric acid-reacting substances (TBARS); C-reactive protein (CRP); interleukin (IL)-6 and the soluble form of its receptor (slL-6R), were evaluated at baseline and after 2 and 3 months of therapeutic intervention. Thirty asymptomatic, untreated individuals with abnormal fasting glycemia, but otherwise healthy status, of similar age, sex, and weight served as control group. RESULTS: At baseline, glycemia (8.83 +/- 0.67mmol/l), HbA1C (8.66 +/- 0.59%), TBARS (8.68 +/- 1.21 micromol/l), CRP (16.05 +/- 3.81 mg/l) IL-6 (5.39 +/- 1.25 pg/ml) and sIL-6R (1425 +/- 492 pg/ml) were significantly higher in diabetic patients than in asymptomatic hyperglycemic individuals (p<0.001). After treatment, glycemia significantly decreased with respect to baseline values (- 9.82% after 60 days and -13.74% after 90 days), as did serum levels of TBARS (-14.05% and -21.89%, respectively), CRP (-32.71% and -43.86%), IL-6 (-23.75% and -40.63%) and sIL-6R (-34.53% and -48.49%, respectively). In diabetic patients, multiple regression showed, at each time, that TBARS and IL-6 were independently correlated with CRP, considering CRP as the dependent variable. Similar correlations were found in asymptomatic hyperglycemic subjects. CONCLUSION: These results suggest that oxidative stress might be implicated in promoting a state of low-grade systemic inflammation in elderly patients with type II diabetes.

Acute-Phase Reaction↗
PubMed2000

Predictive value of nuclear factor kappaB activity and plasma cytokine levels in patients with sepsis.

The relationship between fluctuating cytokine concentrations in plasma and the outcome of sepsis is complex. We postulated that early measurement of the activation of nuclear factor kappaB (NF-kappaB), a transcriptional regulatory protein involved in proinflammatory cytokine expression, may help to predict the outcome of sepsis. We determined NF-kappaB activation in peripheral blood mononuclear cells of 34 patients with severe sepsis (23 survivors and 11 nonsurvivors) and serial concentrations of inflammatory cytokines (interleukin-6, interleukin-1, and tumor necrosis factor) and various endogenous antagonists in plasma. NF-kappaB activity was significantly higher in nonsurvivors and correlated strongly with the severity of illness (APACHE II score), although neither was related to the cytokine levels. Apart from NF-kappaB activity, the interleukin-1 receptor antagonist was the only cytokine tested whose level in plasma was of value in predicting mortality by logistic regression analysis. These results underscore the prognostic value of early measurement of NF-kappaB activity in patients with severe sepsis.

Adult↗
PubMed1999

Circulating cytokine concentrations in tuberculosis and other chronic bacterial infections.

Cytokines are a group of hormone-like polypeptides that play a variety of regulatory roles in host defense against infection. Because of the possible different involvement of these mediators in bacterial infections and tuberculosis, enzyme immunoassay was used to measure comparatively the plasma levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interferon gamma (IFN-gamma) in 25 immunocompetent patients divided into two groups: in 12 patients clinical and microbiological diagnosis showed a chronic bacterial infection and 13 patients had pleuropulmonar tuberculosis. After resolution of the infectious disorders (> or = 3 months), these measurements were repeated for each patient. High levels of IL-1b, TNF-alpha and IL-6 were observed at study entry, but no significant difference was found between the groups. In contrast, plasma levels (mean +/- SEM) of IFN-gamma were significantly higher in patients with tuberculosis when compared with the bacterial group (0.753 +/- 0.201 vs 0.325 +/- 0.105 IU/ml; P = 0.020). This different pattern of plasma proinflammatory cytokines could be ascribed to a prevaling role of the mediators of so-called Th-1 immune response (IFN-gamma) in host defense against infection with Mycobacterium tuberculosis.

Adult↗
PubMed1999

Relationship of plasma leptin to plasma cytokines and human survivalin sepsis and septic shock.

Leptin production is increased in rodents by administration of endotoxin or cytokines. To investigate whether circulating leptin is related to cytokine release and survival in human sepsis, plasma concentrations of leptin, interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, soluble TNF receptor type I, IL-1 receptor antagonist (IL-1ra), and the inflammatory modulator IL-10 were measured as soon as severe sepsis (n=28) or septic shock (n=14) developed and every 6 h for 24 h. Patients with sepsis or septic shock had leptin concentrations 2.3- and 4.2-fold greater, respectively, than the control group. There was an independent association for leptin with IL-1ra and IL-10 in both patient groups. By discriminant analysis, leptin and IL-6 were independent predictors of death. These findings suggest that increases in leptin levels may be a host defense mechanism during sepsis.

Analysis of Variance↗
PubMed1998

Relationship of basal and postprandial intraduodenal bile acid concentrations and plasma cholecystokinin levels with abdominal pain in patients with chronic pancreatitis.

Abdominal pain in patients with chronic pancreatitis has been related to an increase in plasma cholecystokinin (CCK) levels. The aim of the study was to disclose the relation of the altered response with the low intraduodenal bile acids levels found in these patients. Twenty patients with chronic pancreatitis were classified into groups I (n = 11) and II (n = 9) according to the presence or absence of pain. Intraduodenal trypsin and bile acids concentrations and plasma CCK levels were measured before and 30, 60, and 90 min after a test meal. Comparisons between values in both groups were carried out. Correlation of intraduodenal trypsin and bile acids with plasma CCK was analyzed. Patients with pain exhibited significantly lower intraduodenal trypsin levels at 30 and 90 min and lower basal and postprandial intraduodenal bile acids levels than patients without pain. In patients with pain, basal and postprandial plasma CCK levels were significantly higher than in patients without pain. A negative correlation was demonstrated between intraduodenal bile acids and plasma CCK. In patients with chronic pancreatitis and pain, a reduction in intraduodenal postprandial trypsin and basal and postprandial bile acids concentrations, as well as an increase in basal and postprandial plasma CCK levels, was encountered. A negative correlation between intraduodenal bile acids and plasma CCK concentrations was detected that may be implicated in the pathogenesis of pain.

Abdominal Pain↗
PubMed1997

Altered concentrations of appetite regulators may contribute to the development and maintenance of HIV-associated wasting.

OBJECTIVE: To examine the relation of circulating appetite neuropeptides, CCK-8 sulphate (CCK-8s) and beta-endorphin, and the tumour necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNFR) to the anorexia and wasting associated with HIV-infection. DESIGN: Cross-sectional analysis. SETTING: A university-based HIV/AIDS ambulatory clinic in Madrid, Spain. PARTICIPANTS: Thirty-six randomly selected AIDS patients without concomitant diseases or secondary infections were classified into two groups: 19 patients with wasting and 17 with normal body weight, and 18 healthy controls. MEASUREMENTS: Nutritional status was evaluated by anthropometry, laboratory parameters and self-report of appetite. Plasma levels of TNF-alpha and sTNFR proteins p55 (sTNFR-p55) and p75 (sTNFR-p75) were determined by enzyme immunoassay, whereas CCK-8s and beta-endorphin levels were measured by radioimmunoassay. RESULTS: AIDS patients with wasting had significantly higher plasma concentrations of CCK-8s, but lower levels of beta-endorphin when compared to well-nourished AIDS patients (P < 0.01) or controls (P < 0.001). Mean levels of TNF-alpha, and sTNFR-p55 and sTNFR-p75 were greater in AIDS patients with wasting than in asymptomatic AIDS patients or in controls. No significant association was observed between any of these circulating peptides and the parameters of malnutrition. CONCLUSIONS: An activation of the TNF system, together with reciprocal changes in plasma concentrations of two neuropeptides with opposing appetite regulation, that is increased concentrations of CCK-8s but lower levels of beta-endorphin, are associated with the presence of HIV wasting. We hypothesize that these changes may contribute to the development of HIV wasting by producing a pathological inhibition of appetite.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Carbohydrate deficient transferrin and other markers of alcohol consumption in the general hospital].

BACKGROUND: The ascertainment of patients who consume important amounts of alcohol admitted to a hospital is essential to prevent medical and psychological complications. Carbohydrate deficient transferrin (CDT) is a new marker of alcohol consumption which requires validation in the hospital setting. METHODS: The values of carbohydrate deficient transferrin (CDT), glutamic oxalacetic transaminase (GOT), gamma glutamil transpeptidase (GGT) and mean corpuscular volume (MCV) were measured in 101 consecutive patients admitted to the Internal Medicine and Surgery Departments. Considering amounts higher than 60 g/day of ethanol for male patients and higher than 40 g/day for female patients as risk consumption, the values for sensitivity, specificity and area under the curve were calculated for the different biological tests. RESULTS: Twenty-six percent of patients reported a consumption of risk. The sensitivity of the tests were lower than 50% and specificities higher than 77%. CDT had the lowest sensitivity (15%) but it was very specific (98%). CDT had a better sensitivity among women than among men. None of the tests had an area under the curve with adequate efficiency levels. CONCLUSIONS: CDT among the hospitalized patients and other biological markers of alcohol consumption have a low efficiency.

Adult↗
PubMed1996

Postprandial glucose-dependent insulinotropic polypeptide and insulin responses in patients with chronic pancreatitis with and without secondary diabetes.

OBJECTIVE: To study GIP and insulin release after a test meal in patients with chronic pancreatitis with and without secondary diabetes mellitus. METHODS: 28 patients with chronic pancreatitis were classified in groups I and II according to the presence or absence of secondary diabetes mellitus. Twelve healthy subjects were included as controls. After a test meal plasma GIP levels and serum insulin levels were determined at 0, 30, 60, 120 and 180 min. RESULTS: A significant diminished GIP response was found in the groups of patients with respect to the control group. No association could be detected with severity of pancreatic insufficiency. Higher values of GIP were demonstrated at 60 and 120 min in patients without diabetes than in patients with it. CONCLUSIONS: An abnormal GIP response is present in cases of chronic pancreatitis irrespective of the presence or severity of pancreatic insufficiency. This response is further affected if secondary diabetes mellitus is present.

Adult↗
PubMed1996

Relationship between circulating levels of calcitonin gene-related peptide, nitric oxide metabolites and hemodynamic changes in human septic shock.

This study is aimed to investigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in human septic shock. Thirteen patients with septic shock were studied within 6 h after the development of hypotension. Hemodynamic measurements and blood samples were recorded simultaneously at 2-h intervals from study admission. Eighteen normotensive patients with sepsis were included as control group of patients. On study entry, circulating levels of endotoxin did not relate to either CGRP or nitrite and nitrate plasma values. Septic shock patients had significantly higher plasma CGRP, and nitrite and nitrate concentrations, at each of the four time points, than patients with sepsis, as well as both groups of patients compared to normal subjects. No differences were found in plasma SP levels between the two groups of patients. For pooled data from all septic shock patients and measurements (n = 52), both plasma concentrations of CGRP and nitrite and nitrate were inversely correlated, independently from each other, to systemic vascular resistance. On study admission and at 2-h intervals, plasma CGRP concentrations correlated directly with nitrite and nitrate values. Our observations, thus, point to CGRP acting in concert with NO as important mediators responsible for hypotension in human septic shock.

Adult↗
PubMed1996

Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha production by whole blood cells from healthy young and old subjects.

In the present study, we have investigated the effect in vitro of gastrin-releasing peptide (GRP, 10(-10) M), neuropeptide Y (NPY, 10(-10) M), somatostatin (10(-10) M) and vasoactive intestinal peptide (VIP, 10(-9) M) on the production of IL-1 beta, IL-6 and TNF alpha by peripheral whole blood cells from healthy young and old people. We have found that GRP, NPY, somatostatin and VIP stimulated the production of IL-1 beta in old subjects, and NPY, somatostatin and VIP in young ones. In addition, the production of IL-6 was enhanced by GRP, NPY and VIP in young and old people. The TNF alpha production was stimulated by NPY and somatostatin in young subjects, and by NPY, somatostatin and VIP in old ones, whereas GRP produced a decrease of TNF alpha in young persons. GRP in old subjects and VIP in young and old subjects stimulated in a great degree the LPS-induced IL-6 production by whole blood cells. On the contrary, GRP and VIP inhibited highly the LPS-induced TNF alpha production in young controls. Our results show that these neuropeptides, when added to whole blood cells at physiological concentrations, are able to stimulate the production of IL-1 beta, IL-6 and TNF alpha in a differential way according to the subject age.

Adult↗
PubMed1995

Changes in plasma concentrations of vasoactive neuropeptides in patients with sepsis and septic shock.

The aim of this work was to study the hypothesis that the release of vasoactive neuropeptides may be related to the hemodynamic changes and severity of disease in human sepsis and septic shock. Twenty-two patients diagnosed with sepsis and treated in medical wards with standard supportive therapy and twenty patients admitted to a medical intensive care unit because of septic shock were studied Twenty healthy volunteers in a similar age range were enrolled as control group. Blood samples were taken at onset and every 12 hours on the following day after hospital admission to measure plasma concentrations of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and substance P (SP). Clinical and biochemical variables were measured simultaneously. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated on admission. From the day of admission, septic shock patients had significantly higher plasma CGRP-like immunoreactivity levels than patients with sepsis, as well as both groups of patients compared to control subjects. Plasma NPY-like immunoreactivity levels in patients with either sepsis or septic shock was significantly increased, and plasma SP-like immunoreactivity levels significantly reduced compared to those in controls. Plasma CGRP levels at study entry correlated with the APACHE II score (r = 0.71, p < 0.01), as well as with the cardiac index (r = 0.61, p < 0.05) and systemic vascular resistance index (r = -0.62, p < 0.05). Our data suggest that both CGRP and NPY, but not SP, are increasedly released into the circulation during the development of human sepsis and septic shock. In patients with sepsis the vasoconstriction mediated by the release of NPY appears to counterbalance the vasodilatory effect of CGRP. In septic shock patients, however, the release of NPY might be inadequately low to overcome the widespread CGRP-induced vasodilation.

Adult↗
PubMed1995

[Kawasaki's syndrome in the adult and bilateral sacroiliitis].

We present the case of a 23 year old patient with Kawasaki syndrome which resolved without sequelae after salicylate treatment. An peculiar finding was that of typical symptoms and signs of bilateral sacroiliitis demonstrated by symmetrically increased articular uptake of technetium 99 diphosphonate. This sacroiliitis disappeared completely after resolution of the syndrome. HLA-B27 ag was negative. Articular affection in Kawasaki syndrome comprises pain and/or swelling of large and small peripheral joints. Acute sacroiliitis is a finding not previously described. We believe this to have been an isolated episode and not the onset of a chronic seronegative spondylarthritis.

Adult↗
PubMed1994

Cell-mediated immune response and cytokine production in idiopathic senile anorexia.

Some aspects of humoral and cell-mediated immunity and the capacity of peripheral blood mononuclear cells (PBMCs) of fourteen elderly persons with idiopathic anorexia to produce several cytokines, such as tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 and interferon-gamma (IFN gamma), were studied and the results were compared with those obtained in a control group of ten age-matched, normal weight healthy subjects. In addition, spontaneous and induced production of these cytokines was also measured in cultures of PBMCs of fourteen healthy young individuals as a control group of age. A significant decrease in CD2 (pan T-cells) and CD4 (T-helper) lymphocyte subpopulations, but unchanged CD8 (T-suppressor) subset, and a reduced response in delayed cutaneous hypersensitivity tests were observed in senile underweight anorectic patients. Monocyte counts did not show significant differences between patients and control subjects. The spontaneous release by PBMCs of all the cytokines measured did not differ between the anorectic and either the elderly or young control group. A significant increase in IL-6 production after mitogen stimulation with tetradecanoylphorbol acetate (TPA) and phytohemagglutinin (PHA) after 24 and 48 h of culture, as well as a greater induced TNF alpha production after 48 h of incubation with the same mitogens, was found in the anorectic patients as compared with the elderly controls. However, stimulated production of both IL-1 beta with TPA and of IFN gamma with PHA did not differ significantly between anorectics and aged controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗