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Biomedical subjects

C Guijarro

Publications and source records attributed to C Guijarro.

At least 37 records · Page 2Linked to original sources
PubMed1997

Relapse of tuberculosis after treatment in human immunodeficiency virus-infected patients.

OBJECTIVES: To evaluate the relapse rate of tuberculosis after a complete course of antituberculous therapy in human immunodeficiency virus-infected patients and to identify the risk factors for relapse. PATIENTS AND METHODS: Historic cohort study of all adult patients who were diagnosed as having human immunodeficiency virus infection and a first episode of culture-proved tuberculosis at 2 university hospitals in Madrid, Spain, between 1986 and 1992, and who completed at least 6 months of treatment were included and followed up until September 1994. RESULTS: Of 276 patients with human immunodeficiency virus infection and tuberculosis, 87 could not be evaluated (6 died before treatment, 39 died during treatment, 36 did not complete the planned therapy, and 6 were unavailable during treatment). The remaining 189 received a standard regimen (ie, 3 or 4 drugs, always including rifampin and isoniazid, for > or = 6 months). The median duration of follow-up for these 189 patients was 31.5 months, with a total of 4668 patient-months of follow-up after treatment; 105 patients (56%) were followed up until death. The relapse rate was 7.9% (2.7/100 patient-years). With multivariate analysis, a shorter duration of treatment and a low CD4+ cell count were associated with a greater probability of relapse. Relapses occurred in 5 (3.4%) of 148 patients who were treated for 9 or more months (1.7/100 patient-years) and in 10 (24%) of 41 patients who were treated for less than 9 months (10.9/100 patient-years) (P < .001; relative hazard, 9.2; 95% confidence interval, 3.1-26.9). CONCLUSIONS: As standard antituberculous therapy for 9 months is associated with a low rate of relapse, maintenance therapy is not required. Duration of treatment for less than 9 months is associated with a high rate of relapse.

AIDS-Related Opportunistic Infections↗
PubMed1997

Increased lipoproteins and fibrinogen in chronic renal allograft dysfunction.

Chronic rejection - also called chronic renal allograft dysfunction (CRAD) - is the main cause of long-term loss of the transplanted kidney, but its pathogenesis is not well known. The aim of this study was to know if lipoproteins, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and platelet aggregation show more abnormalities in renal transplant patients with CRAD than in those with stable renal function. Sixty patients with renal allograft have been studied; 20 patients with CRAD and 40 controls matched for age, gender and time after transplantation. In a univariate analysis patients with CRAD had higher total serum triglycerides (214+/-153 vs. 133+/-39 mg/dl; p = 0.04) and very-low-density lipoprotein (VLDL) triglycerides (128+/-116 vs. 59+/-29 mg/dl; p = 0.04). Apolipoprotein B levels were also increased in patients with CRAD although this difference was only borderline significant (131+/-58 vs. 98+/-16 mg/dl; p = 0.05). Similarly, there was a trend toward increased total, VLDL, and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol in CRAD patients, but these differences did not reach statistical significance. Apolipoprotein A-1 and lipoprotein(a) levels were similar in both groups. Neither platelet aggregation nor PAI-1 levels differed between both groups. In contrast, fibrinogen was increased in patients with CRAD (373+/-81 vs. 322+/-62 mg/dl; p = 0.01). In a multivariate analysis triglycerides and fibrinogen were positively correlated to CRAD. These findings add further support to the hypothesis that lipid abnormalities may be involved in the pathophysiology of CRAD. In addition, this is the first report showing that fibrinogen levels are increased in patients with CRAD. Further studies are needed to evaluate a potential role of fibrinogen in the development of CRAD.

Adult↗
PubMed1996

Serum albumin and mortality after renal transplantation.

The incidence, causes, and consequences of hypoalbuminemia after renal transplantation are not well defined. We examined clinical correlates of serum albumin measured at 3 months, 6 months, 1 year, and annually thereafter in 706 renal transplant recipients who survived at least 6 months with a functioning allograft. Follow-up was 7.0 +/- 4.2 years. Hypoalbuminemia (< or = 3.5 g/dL) was most common at 3 months (31%, n = 692), least common at 1 year (12%, n = 656), and then became increasingly common among survivors, for example, 14% (n = 466) at 4 years, 20% (n = 204) at 8 years, and 29% (n = 77) at 12 years after transplantation. By multiple linear regression, variables that correlated (P < 0.05) with lower serum albumin at 3, 6, 12, and 24 months included age, diabetes, proteinuria, and cytomegalovirus infection. Other independent correlates on at least one of these occasions included renal function and chronic disease (malignancy, liver disease, and cardiovascular disease). Serum albumin, as a time-averaged and time-dependent covariate, was a strong independent risk factor for death using Cox proportional hazards analysis (relative risk for each g/dL increment, 0.26; 95% confidence interval, 0.16 to 0.44 [1.00 = no risk]). The effects of albumin on mortality were independent of age, diabetes, serum lipids, renal function, chronic liver disease, malignancies, and cardiovascular disease. The effects of albumin on mortality were evident even when the analysis was restricted to patients dying several years after albumin was measured. Thus, hypoalbuminemia is common and serum albumin is a strong independent risk factor for all-cause mortality after renal transplantation.

Actuarial Analysis↗
PubMed1996

Chronic renal allograft rejection: immunologic and nonimmunologic risk factors.

The pathogenesis of chronic renal allograft rejection is unknown. It is also unclear why cyclosporine has failed to prevent chronic rejection. We examined possible risk factors for graft loss to chronic rejection among 706 renal transplants using the Cox proportional hazards model with fixed and time-dependent covariates. Both the number and the severity of acute rejection episodes were independent risk factors for chronic rejection [relative risk (95% confidence interval) 2.31 (2.04 to 2.60) and 1.53 (1.27 to 1.84), respectively]. Cyclosporine and cyclosporine withdrawal had no effect on chronic rejection. Acute rejections occurring within the first three months after transplantation, when cyclosporine most effectively prevented acute rejection, also had no effect on chronic rejection. Risk factors that were independent of acute rejection and not clearly attributable to immune mechanisms included serum albumin [0.20 (0.10 to 0.38) for each g/dl], proteinuria [1.42 (1.29 to 1.57) for each g/24 hr], and serum triglycerides -1.09 (1.03 to 1.16) for each 100 mg/dl-. These results suggest that the reduction in acute rejection episodes from cyclosporine has failed to reduce graft failure from chronic rejection, possibly because the early (within the first 3 months) and mild acute rejection episodes that are most effectively prevented by cyclosporine do not cause chronic rejection. In addition, the results suggest that there may be a number of nonimmunologic risk factors for chronic rejection.

Adolescent↗
PubMed1996

Expression of leucocyte chemoattractants by interstitial renal fibroblasts: up-regulation by drugs associated with interstitial fibrosis.

Interstitial inflammation is a strong predictor of long-term renal damage. The potential role of renal interstitial fibroblasts in recruitment of inflammatory leucocytes into the interstitium is unclear. We have thus studied the mRNA expression of several leucocyte chemotactic factors by rat renal interstitial fibroblasts and its modulation by cytokines. In addition, the effects of two unrelated drugs associated with the development of interstitial fibrosis, namely puromycin aminonucleoside (PAN) and cyclosporin A (CsA), were also studied. Rat renal interstitial fibroblasts showed constitutive mRNA expression for the chemokines monocyte chemoattractant protein 1 (MCP-1) and interferon-inducible protein 10 (IP-10). In addition, these cells also exhibited constitutive mRNA expression for cyclophilin B, an immunophilin recently found to have leucocyte chemoattractant properties. The inflammatory cytokine tumour necrosis factor-alpha up-regulated IP-10 and MCP-1 mRNA expression (10- and four-fold, respectively), but had no effect on cyclophilin B mRNA levels. IP-10 and MCP-1 produced about a four-fold increase in MCP-1 and cyclophilin B mRNA expression, but did not affect IP-10 mRNA. PAN caused an augmentation in IP-10, MCP-1 and cyclophilin B mRNA levels (12-, 9.5, and two-fold, respectively), while CsA increased only cyclophilin B mRNA in a dose-dependent manner. In conclusion, rat renal interstitial fibroblasts express mRNA for chemotactic factors and this expression is up-regulated by inflammatory cytokines, PAN and CsA. The present findings suggest that renal interstitial fibroblasts may play an active role in the recruitment of inflammatory leucocytes into the interstitium.

Animals↗
PubMed1996

Cardiovascular disease after renal transplantation.

Although cardiovascular disease is a major cause of morbidity and mortality after renal transplantation, its pathogenesis and treatment are poorly understood. We conducted separate analyses of risk factors for ischemic heart disease, cerebral, and peripheral vascular disease after 706 renal transplants, all of which functioned for at least 6 months. We used Cox proportional hazards analysis to examine the effects of multiple pretransplant and posttransplant risk factors and included time-dependent variables measured at 3, 6, and 12 months, and annually to last follow-up at 7.0 +/- 4.2 yr. The independent relative risk (RR) of diabetes was 3.25 for ischemic heart disease, 3.21 for cerebral vascular disease, and 28.18 peripheral vascular disease (P < 0.05). The RR of each acute rejection episode was 1.40 for ischemic heart disease and 1.24 for cerebral vascular disease. Among serum lipid levels, high-density lipoprotein cholesterol was the best predictor of ischemic heart disease (RR = 0.80 for each 10 mg/dL). Posttransplant ischemic heart disease was strongly predictive of cerebral (5.80) and peripheral vascular disease (5.22), whereas ischemic heart disease was predicted by posttransplant cerebral (8.25) and peripheral vascular disease (4.58). Other risk factors for vascular disease included age, gender, cigarette smoking, pretransplant splenectomy, and serum albumin. Hypertension and low-density lipoprotein cholesterol had no effect, perhaps because of aggressive pharmacologic treatment. Thus, the incidence of cardiovascular disease continues to be high after renal transplantation, and multiple risk factors suggest a number of possible strategies for more effective treatment and prevention.

Adult↗
PubMed1996

Lovastatin inhibits lipopolysaccharide-induced NF-kappaB activation in human mesangial cells.

BACKGROUND: HMG-CoA reductase inhibitors have been shown to reduce glomerular injury in different models of progressive renal damage. The transcription factor NF-kappaB plays a major role in the induced expression of genes involved in cellular proliferation and inflammatory responses that could be important in the pathogenesis of glomerular injury. We therefore examined the effects of the HMG-CoA reductase inhibitor lovastatin on NFkappaB activation in human mesangial cells. METHODS: Cultured human mesangial cells were stimulated with bacterial lipopolysaccharide (LPS) in the presence or absence of lovastatin. NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: LPS-stimulated mesangial cells exhibited an NF-kappaB-like activity as assessed by EMSA competition assays, and supershift assays with antibodies against the p50 and p65 subunits of NF-kappaB. Treatment of mesangial cells with lovstatin in the presence of exogenous cholesterol resulted in a significant reduction of the LPS-induced NF-kappaB activity. In the presence of either mevalonate or the mevalonate metabolite farnesyl pyrophosphate, the lovastatin inhibition of NF-kappaB activation was substantially reversed, supporting a role for mevalonate metabolites in LPS-induced mesangial cell NF-kappaB activation. CONCLUSIONS: These data suggest an additional mechanism by which HMG-CoA reductase inhibitors may reduce glomerular injury, namely, by inhibiting NF-kappaB activation and the subsequent proliferative and inflammatory responses.

Base Sequence↗
PubMed1996

Effects of lipids on the pathogenesis of progressive renal failure: role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in the prevention of glomerulosclerosis.

Increasing experimental evidence suggests that lipids might be important modulators in progressive glomerulosclerosis. The inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase have demonstrated beneficial effects in different models of progressive renal failure. Monocyte infiltration, mesangial cell proliferation and mesangial matrix expansion have been shown to be early events in the process of glomerulosclerosis that can be lessened by HMG-CoA reductase inhibition. Recent experimental data suggest that these agents may also have glomerular protective effects independent of a reduction in circulating lipids. In vitro, lovastatin has been shown to downregulate mesangial cell production of monocyte chemoattractant protein-1 and colony-stimulating factor. In addition, HMG-CoA reductase inhibitors can directly reduce mesangial cell proliferation. These effects appear related to the ability of this class of agents to inhibit mesangial cell formation of intermediates of cholesterol formation, the nonsterol isoprenoids. Although low density lipoprotein cholesterol can induce mesangial cells to increase synthesis of matrix proteins, e.g., type-IV collagen, we have shown that lovastatin does not directly influence mesangial cell type-IV collagen metabolism. Thus, prevention of mesangial matrix expansion in vivo with type-IV collagen by HMG-CoA reductase inhibitors could be related to an indirect mechanism related to inhibition of monocyte influx into the glomerulus. Alternatively, a direct effect of these agents, through their cholesterol-lowering capabilities, could play a role in reducing matrix expansion.

Animals↗
PubMed1995

Modulation of glycogen phosphorylase activity and fructose 2,6-bisphosphate levels by glibenclamide and meglitinide in isolated rat hepatocytes: a comparative study.

The influence of glibenclamide and meglitinide, or 4-[2-(5-chloro-2-methoxybenzamide)ethyl]-benzoic acid, a compound similar to the nonsulfonylurea moiety of glibenclamide, on glycogen phosphorylase a activity, fructose 2,6-bisphosphate (F-2,6-P2) level, and cytoplasmic free-Ca2+ concentration has been studied in isolated rat hepatocytes. Both glibenclamide and meglitinide caused a transient and dose-dependent activation of glycogen phosphorylase, with half-maximal effects corresponding to 3.7 +/- 1.6 and 9.6 +/- 3.3 mumol/L, respectively. This enzyme activation occurred without significant changes in hepatocyte cyclic adenosine monophosphate (cAMP) levels and was accompanied by an increase in cytoplasmic concentration of free Ca2+. Parallel to these effects, glibenclamide increased the cellular content of F-2,6-P2, with this effect being associated with a reduction in the rate of glucose formation from a mixture of [14C]lactate/pyruvate. Under similar conditions, meglitinide caused a significant reduction of F-2,6-P2 levels and accelerated the gluconeogenic flux. The mechanism by which meglitinide decreases hepatocyte F-2,6-P2 levels seems to be mediated by stimulation of fructose-2,6-bisphosphatase. This comparative study may help to elucidate which among the hepatic effects of glibenclamide are exerted specifically by the sulfonylurea moiety.

Adenine Nucleotides↗