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Biomedical subjects

C Guijarro

Publications and source records attributed to C Guijarro.

At least 19 recordsLinked to original sources
PubMed2006

Mortality among adult patients admitted to the hospital on weekends.

BACKGROUND: Some reports have shown that the risk of death is higher for patients admitted on weekends than for patients who go into the hospital on weekdays. This study was conducted to assess what independent influence, if any, weekend admission might have on mortality in our hospital. METHODS: The clinical data of 35,993 adult (>14 years) patients admitted to the emergency department of Fundación Hospital Alcorcón from 1999 to 2003 were analyzed. We compared global mortality and mortality within the first 48 h according to whether the patients were admitted on the weekend or on a weekday. Elective admissions, critical care patients, children under 14 and births were not included. RESULTS: Global mortality was similar in both groups, but mortality within the first 48 h was higher for patients admitted on the weekend (OR 1.40, 95% CI 1.18-1.62, P<0.001), even after controlling for age, gender and comorbidity (weight of diagnosis-related group and Charlson comorbidity index). CONCLUSION: The risk of mortality within the first 48 h is higher for patients admitted on weekends than for patients admitted on a weekday.

Journal Article↗
PubMed2005

Occult vascular lesions in patients with atherothrombotic events: the AIRVAG cohort.

OBJECTIVES: To determine clinical parameters that could predict occult vascular lesions (OVL) in patients with symptomatic atherosclerosis. PATIENTS AND METHODS: Prospective evaluation of 269 consecutive patients with symptomatic atherosclerosis (cerebral 32%, peripheral vascular 15%, and coronary 53%): complete laboratory, ultrasound exams (carotids, aorta, heart), ankle-brachial index. OVL were defined as: abdominal aortic aneurysm, carotid artery stenosis > 50%, or left ventricular segmental contraction abnormalities when affecting a different vascular bed from the symptomatic. Clinical predictors of OVL were evaluated by logistic regression analysis. RESULTS: OVL were found in 35 patients (13%): 12 abdominal aortic aneurysms, 21 carotid artery stenosis and 15 segmental left ventricular contraction abnormalities. OVL were associated with peripheral vascular disease (intermittent claudication or reduced ankle-brachial index), cigarette smoking, increased pulse pressure, microalbuminuria and hyperhomocysteinemia. By multivariate analysis, intermittent claudication (odds ratio 5.8; 95% CI 2.6-12.8) and microalbuminuria (OR 4.2; 95% CI 1.7-10.5) were strong independent predictors of OVL. Similar results were obtained when peripheral vascular disease was defined as reduced ankle-brachial index (OR 5.3; 95% CI 2.4-11.7). CONCLUSIONS: Clinical and subclinical peripheral vascular disease, as well as microalbuminuria are strong independent predictors of OVL in atherosclerotic patients. A screening study of OVL may be warranted in these patients.

Albuminuria↗
PubMed2002

Assessing clinical probability of organic disease in patients with involuntary weight loss: a simple score.

BACKGROUND: Involuntary weight loss (IWL) is a frequent complaint with a difficult diagnosis. Any one of a number of different diseases may be the source of the symptom. However, there is no universal clinical protocol that can help physicians study this complex syndrome. METHODS: In March 1998, we defined a diagnostic protocol for the study of IWL. IWL was defined as an involuntary and documented weight loss of at least 5% of the usual body weight in the previous 3 months. We analyzed 78 consecutive patients with IWL who came to our clinic between March 1998 and December 2000. RESULTS: An organic disease was found in 56% of cases; cancer, metabolic and digestive diseases were the most common entities. Psychiatric problems were found in 33% of cases. After extensive study, an idiopathic group of 11% was identified. The variables that were independently predictive of a final diagnosis of organic disease were: age>50 years (OR: 8.6, CI 95%: 1.7-43.6), psychiatric symptoms (OR: 0.2, CI 95%: 0.1-0.8), smoking (OR: 14.3, CI 95% 2.3-74), the presence of guide symptoms (OR: 8.0, CI 95%: 1.8-34.4), and anemia (OR: 3.1, CI 95%: 2.5-387). Sixteen percent of the patients died, more often those suffering from organic diseases. Based on multivariate regression coefficients, a clinical risk score was established. CONCLUSIONS: IWL is a complex and frequent syndrome with a 16% rate of mortality during the first year. A protocol based on clinical data can help in the management of IWL. Our clinical prediction rule may help physicians to identify those patients with IWL who are likely to have an underlying organic disease.

Journal Article↗
PubMed2001

Transcription factor-kappa B (NF-kappa B) and renal disease.

Transcription factor-kappa B (NF-kappa B) and renal disease. Nuclear factor-kappa B (NF-kappa B) comprises a family of dimeric transcription factors that regulate the expression of numerous genes involved in inflammation and cell proliferation. Although NF-kappa B was initially identified in lymphocytes, it has been found to be a transcription factor present in virtually all cell types. In resting cells, NF-kappa B dimers remain in the cytoplasm in an inactive form bound to the inhibitory subunit I kappa B. Upon stimulation, I kappa B is phosphorylated, ubiquitinylated, and ultimately degraded by proteolytic cleavage by the proteasome system. As a result, NF-kappa B dimers are translocated into the nucleus and activate the transcription of target genes. Increasing data suggest a pivotal role for NF-kappa B in a variety of pathophysiological conditions in which either inflammation or cell number control are critical events. NF-kappa B has been found to be activated in experimental renal disease. Importantly, both in vivo and in vitro, NF-kappa B activation can be modulated by pharmacological maneuvers. Indeed, it is now widely acknowledged that the anti-inflammatory action of steroids is basically obtained through the inhibition of the transactivation of NF-kappa B-dependent genes. In addition, some of the beneficial effects of angiotensin-converting enzyme inhibitors and statins may, at least in part, be mediated by an inhibition of NF-kappa B activation. A better understanding of the mechanisms involved in NF-kappa B regulation and its modulation may provide new tools to improve the treatment of renal diseases with a better sound pathophysiological approach.

Animals↗
PubMed2000

Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin.

Low-density lipoprotein (LDL) may contribute to the pathogenesis of glomerulosclerosis by stimulating a mesangial cell inflammatory response. Interleukin-6 (IL-6) is a marker of active inflammation and ongoing glomerular injury. Therefore, we investigated the effects of native and oxidized LDL on human mesangial cell production of IL-6 and a possible modulation of this inflammatory response by lovastatin, which has been shown to ameliorate experimental glomerulosclerosis. Human mesangial cells were exposed for 6 or 24 h to culture medium containing either native LDL alone or a LDL mixture containing 5 or 20% oxidized LDL. We found that native LDL stimulated 6 h mRNA expression and secretion of IL-6. This effect was further enhanced, in a dose-related manner, when mesangial cells were exposed to increasing concentrations of oxidized LDL. Lovastatin markedly inhibited mesangial cell expression of IL-6 mRNA and reduced IL-6 secretion. The inhibitory effects of lovastatin were overridden at least partially by exogenous mevalonate. We conclude that LDL, and particularly oxidized LDL, might contribute to the pathogenesis of glomerular disease by modulating the inflammatory response of human mesangial cells, as assessed by the stimulation of IL-6 expression. Moreover, this inflammatory response can be prevented by lovastatin, providing a potential direct anti-inflammatory mechanism by which HMG-CoA reductase inhibitors may attenuate lipid-induced glomerular injury.

Base Sequence↗
PubMed1999

The central role of nuclear factor-kappa B in mesangial cell activation.

BACKGROUND: Nuclear factor-kappa B (NF-kappa B) is a family of transcription factors that is recognized by the kappa B enhancer element. Numerous proinflammatory genes have binding sites for NF-kappa B, and the products of these genes are an integral part of cellular activation and inflammatory response systems. Because there is a close relationship between NF-kappa B and mediators of cell activation, it is possible that a disruption of NF-kappa B-activating pathways may effectively influence mesangial cell activation. METHODS: We reviewed available studies related to both NF-kappa B and mesangial cells in order to provide evidence for the role of NF-kappa B in mesangial cell activation. RESULTS: Studies reported by this laboratory and others showed that various experimental maneuvers that modulate NF-kappa B activation result in a parallel modulation of proinflammatory molecule production in cultured mesangial cells. Likewise, the ability of the inhibitors of NF-kappa B activation to down-regulate the inflammatory response in animal models of renal disease has been recently demonstrated. CONCLUSIONS: These data suggest a pivotal role of NF-kappa B in mesangial cell activation and designate it as an obvious target for the modulation of this activation. Studies are necessary to characterize the role of NF-kappa B in human renal injury.

Animals↗
PubMed1999

Importance of geranylgeranyl pyrophosphate for mesangial cell DNA synthesis.

BACKGROUND: Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are isoprenoid products of the intracellular mevalonate pathway used for prenylation of several low molecular weight G proteins, including Ras. It is likely that platelet-derived growth factor (PDGF) stimulation of mesangial cell proliferation requires prenylated, low molecular weight G proteins. The purpose of this study was to investigate the dependence of platelet-derived growth factor-stimulated mesangial cell DNA synthesis and cell membrane Ras incorporation on FPP and GGPP. METHODS: Quiescent human mesangial cells were exposed to PDGF (25 ng/ml) to stimulate DNA synthesis. Some cells were also treated with the HMG-CoA reductase inhibitor lovastatin (2.5 to 10.0 microM), which inhibits isoprenoid synthesis, in the presence or absence of exogenous FPP or GGPP. DNA synthesis was assessed by thymidine incorporation, and Western blot analysis was used to measure total cell membrane Ras. RESULTS: Stimulation of mesangial cells with PDGF did not increase total cell membrane Ras. Lovastatin reduced cell membrane Ras, and this was prevented by simultaneous exposure of mesangial cells to exogenous FPP (2.5 to 10.0 microM) or GGPP (1 to 5 microM). Lovastatin also reduced PDGF-stimulated mesangial cell DNA synthesis by 90%, and this was completely prevented by simultaneous exposure of cells to exogenous GGPP (1 microM), but not to FPP. CONCLUSIONS: The results of this study suggest that both FPP and GGPP can provide for mesangial cell membrane Ras localization and that PDGF-stimulated mesangial cell DNA synthesis requires the isoprenoid GGPP.

Blotting, Western↗
PubMed1999

Lipophilic statins induce apoptosis of human vascular smooth muscle cells.

BACKGROUND: The accumulation of vascular smooth muscle cells (VSMC) in the intima is an early feature of atherosclerosis that results from a balance of migration from the media, proliferation, and eventual death (including programmed cell death) of VSMC. Several reports have described that HMG-CoA reductase inhibitors (statins) attenuate both the migration and proliferation of VSMC. However, the potential effect of statins on VSMC programmed cell death has received little attention. METHODS: Human and rat VSMC were incubated with different concentration of statins in the presence of fetal bovine serum as a survival factor. The presence of apoptosis was evaluated by morphological criteria, flow cytometry and DNA electrophoresis. RESULTS: Lipophilic statins induced, in a dose-dependent manner the appearance of VSMC apoptosis. The effect of statins was fully reversed by mevalonate, farnesylpyrophosphate, and geranylgeranypyrophosphate, but not by cholesterol or other mevalonate metabolites, suggesting a role for isoprenoids in VSMC apoptosis. In addition, the induction of apoptosis by statins was associated with the inhibition of prenylation of Rho B. CONCLUSIONS: The present results suggest that protein prenylation inhibition by statins may be involved in statin-induced VSMC apoptosis. These data provide a new potential mechanism by which statins may modulate the evolution of atherosclerotic lesions.

Animals↗
PubMed1998

3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.

Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to induce apoptosis in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis of VSMCs, cultured rat VSMCs were treated with increasing doses of atorvastatin in the presence of FBS as a survival factor. The presence of apoptosis was evaluated by morphological criteria, annexin V binding, and DNA fragmentation and quantified as the proportion of hypodiploid cells by flow cytometry. Atorvastatin induced apoptosis in a dose-dependent manner, an effect also seen with simvastatin and lovastatin, but not with the hydrophilic drug pravastatin. The proapoptotic effect of statins was seen only when the inhibition of acetate incorporation into sterols was >95% and was fully reversed by mevalonate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate but not by isopentenyl adenosine, ubiquinone, or squalene, suggesting a role for prenylated proteins in the regulation of VSMC apoptosis. To further assess the role of protein prenylation, VSMCs were exposed to the prenyl transferase inhibitors perillic acid and manumycin A. Both agents induced VSMC apoptosis as evaluated by the above-mentioned criteria. Finally, VSMC treatment with lipophilic statins was associated with decreased prenylation of p21-Rho B, further supporting the role of protein prenylation inhibition in statin-induced VSMC apoptosis. The present data suggest that interference with protein prenylation by HMG-CoA reductase inhibitors or other agents may provide new strategies for the prevention of neointimal thickening.

Animals↗
PubMed1998

Lipid abnormalities in stable liver transplant recipients--effects of cyclosporin, tacrolimus, and steroids.

Dyslipidemia is common after liver transplantation, but the underlying mechanisms are largely unknown. We studied the lipid profile of 27 liver transplant recipients randomized to received either cyclosporin (CyA, n = 14) or tacrolimus (n = 13) and compared them with 20 healthy, matched controls. Before transplantation, patients presented low total and low-density lipoprotein (LDL) cholesterol (as compared to controls) that increased shortly, i.e., 3 months, after transplantation. Eighteen months post-transplantation, total and LDL cholesterol levels decreased to pre-transplant values but tended to remain higher in CyA-treated patients. However, at that time, prednisone treatment was more prevalent among CyA-treated than tacrolimus-treated patients and fully accounted for the difference in cholesterol levels. Indeed, regardless of therapy, patients not receiving prednisone exhibited lower cholesterol levels than prednisone-treated patients and controls. We conclude that prednisone therapy, rather than CyA or tacrolimus immunosuppression, seems to be the major determinant of increased cholesterol levels.

Adult↗
PubMed1998

Lovastatin reduces glomerular macrophage influx and expression of monocyte chemoattractant protein-1 mRNA in nephrotic rats.

Glomerular expression of monocyte chemoattractant protein-1 (MCP-1) and subsequent glomerular macrophage infiltration may play an important role in the development of glomerulosclerosis. Previous studies have shown that lovastatin ameliorates experimental renal disease and reduces MCP-1 expression in serum-stimulated, cultured mesangial cells. We investigated the effects of lovastatin on glomerular MCP-1 expression and macrophage infiltration in rats with puromycin aminonucleoside (PA) nephrosis, an experimental model of renal disease characterized by early macrophage infiltration. Male Sprague-Dawley rats were pretreated for 5 days with either lovastatin (4 mg/kg) or vehicle. At the end of pretreatment, the lovastatin-pretreated rats received a single i.v. injection of PA (50 mg/kg) and continued to receive daily lovastatin thereafter. The vehicle-pretreated rats received i.v. injections of either PA or saline, and continued to receive daily vehicle treatment thereafter. Ten days after PA injection, the vehicle-treated PA rats showed increased (P < 0.05) serum cholesterol (359 +/- 25 mg/100 mL) and urine albumin excretion (343 +/- 95 mg/24 hr), compared with the vehicle-treated control rats (61 +/- 3 mg/100 mL and 2.5 +/- 0.6 mg/24 hr, respectively). Serum cholesterol (193 +/- 22 mg/dL) and urine albumin excretion (255 +/- 68 mg/24 hr) were less in the lovastatin-treated PA rats than in the vehicle-treated PA rats. The number of glomerular macrophages, assessed as ED-1-positive cells, per glomerular profile was increased 77% in the vehicle-treated PA rats (3.3 +/- 0.2) compared with the vehicle-treated control rats (1.8 +/- 0.2) (P < 0.05). By contrast, the number of glomerular macrophages was not elevated in the lovastatin-treated PA rats (2.3 +/- 0.2). Thus, lovastatin in vivo can attenuate glomerular macrophage infiltration. This may represent one mechanism by which lovastatin ameliorates experimental glomerular disease.

Animals↗
PubMed1998

Lipoprotein changes in patients with chronic hepatitis C treated with interferon-alpha.

OBJECTIVE: The aim of this study was to evaluate the effects of interferon-alpha therapy on the lipid profile of patients with chronic hepatitis C. METHODS: In 36 consecutive patients with chronic hepatitis C, fasting lipoproteins were evaluated prospectively at baseline, 1, 3 and 6 months during interferon-alpha therapy and 3 months after the end of treatment. RESULTS: During interferon-alpha therapy, there was a progressive increase in total and very low density lipoprotein (VLDL)-triglycerides, VLDL-cholesterol and a sustained raise in apolipoprotein (apo) B. In parallel, there was a reduction in high density lipoprotein (HDL)-cholesterol and apo A1 levels. In contrast, total and low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels remained essentially unchanged during interferon-alpha therapy. Three patients developed chylomicronemia, two of them with severe hypertriglyceridemia, although none of them presented with pancreatitis. Chylomicronemia and severe hypertriglyceridemia were more common in patients with basal triglycerides above 200 mg/dl. Nineteen patients responded to interferon-alpha therapy, but their lipid profile did nor differ from that of nonresponders. Three months after the end of interferon-alpha therapy lipid changes subsided, although VLDL and HDL-cholesterol and apo B did not reach basal levels. CONCLUSION: In patients with chronic hepatitis C, interferon-alpha therapy is associated with an increase of total and VLDL-triglycerides, VLDL-cholesterol and apo B, and a decline of HDL-cholesterol and apo A1. The development of chylomicronemia and severe hypertriglyceridemia in some cases makes mandatory a close monitoring of triglycerides during interferon-alpha therapy, particularly among patients with increased triglycerides at baseline.

Adult↗
PubMed1998

Lipoprotein abnormalities in long-term stable liver and renal transplanted patients. A comparative study.

Hyperlipidemia is a common feature after organ transplantation. Most studies have evaluated the lipid profile in recipients of a particular graft, usually renal. In the present work, we studied the lipid profiles of 30 long-term stable liver transplant patients (LTP) and compared their pattern with 40 long-term stable renal transplant patients (RTP) matched for gender, age, and time from transplantation. There were no significant differences between both groups in body mass index, serum glucose, serum creatinine, or urinary protein excretion. In contrast, RTP had higher pre-transplant total cholesterol and triglycerides, received higher doses of steroids (both average and cumulative) and had higher cycosplorine blood levels. After a mean time of 60 months after transplantation, RTP exhibited higher levels of total serum cholesterol (226 +/- 26 vs. 180 +/- 39 mg/dl; p = 0.000 002) and low-density lipoprotein (LDL) cholesterol (152 +/- 22 vs. 112 +/- 37 mg/dl; p = 0.00001). In contrast, there were no differences between RTP and LTP in high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides, or lipoprotein (a) [Lp(a)]. By univariate analysis in the whole group, renal graft, prednisone daily dose, cyclosporine blood levels, pre-transplant cholesterol, and triglycerides were associated with increased post-transplant cholesterol levels. By multivariate analysis, prednisone daily dose was the only independent variable predicting increased post-transplant serum cholesterol levels. The present data show that hypercholesterolemia is more frequent among RTP than among LTP. In addition, our data suggest that corticosteroid therapy, rather than the transplanted organ, may be the major contributor to this difference.

Adult↗