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Biomedical subjects

J A Gutiérrez

Publications and source records attributed to J A Gutiérrez.

At least 19 recordsLinked to original sources

[Self-limited thrombotic microangiopathy associated with perianal abscess].

A 43-year-old female with Staphyloccocus-induced perianal abscess, was admitted to hospital because of a clinical picture of acute renal failure and thrombotic microangiopathy. Schistocytes, thrombopenia, a negative Coombs test and no detectable plasma haptoglobin were diagnostic for thrombotic microangiopathy. Antibiotics, surgical drainage, plasmapheresis and fresh frozen plasma were given with a favourable evolution. We review the prognostic factors determining recovery of renal function and hematological abnormalities.

Abscess↗

Concomitant use of policosanol and beta-blockers in older patients.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. It is safe and well tolerated, even in populations with high consumption of concomitant drugs. These data suggest that adverse events (AE) due to drug-to-drug interactions (DDI) with policosanol are not relevant. Experimental data indicate that potential DDI between policosanol and drugs metabolized through the cytochrome P450 hepatic system are not expected, but pharmacodynamic DDI cannot be excluded. Several clinical studies have shown that policosanol decreased arterial pressure compared with placebo, and a pharmacological interaction with beta-blockers was experimentally proven. Therefore, clinical DDI between policosanol and beta-blockers can be expected. This study investigated whether policosanol reinforces the antihypertensive effects of beta-blockers and/or whether this combination impairs some safety indicators or induces specific AE in older patients. After 5 weeks on a diet-only baseline period, 205 older hypercholesterolemic patients taking beta-blockers were randomized to policosanol 5 mg/day or placebo for 3 years. After 1 year on therapy, policosanol significantly reduced (p < 0.00001 versus placebo) low-density lipoprotein-cholesterol (LDL-C) (20.9%), total cholesterol (TC) (19.3%) and triglycerides (TG) (25.7%), whereas it increased (p < 0.01 and p < 0.001 versus placebo) high-density lipoprotein-cholesterol (HDL-C) levels (4.1%). Treatment effects did not to wear off during the 3-year follow-up. At study completion, policosanol lowered (p < 0.00001 versus placebo) LDL-C (34.3%), TC (23.2%) and TG (21.2%) and raised (p < 0.00001 versus placebo) HDL-C (12.3%). Thirty-one patients (15.1%) discontinued the study, 22 in the placebo group (20.6%) and nine in the policosanol group (9.2%). Of these, 20 patients (16 in the placebo group and four in the policosanol group) withdrew from the study due to AE. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (3/98, 3.1%) was lower than in the placebo group (15/107, 14.0%). No impairment of safety indicators was observed. Nevertheless, reductions in systolic and diastolic blood pressure were observed in policosanol patients compared with those in the placebo group. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). In conclusion, policosanol was well tolerated in elderly patients taking beta-block- ers and did not increase AE. Additional reduction of blood pressure and a lower frequency of SAE were observed in policosanol patients compared with those taking placebo. The cholesterol-lowering efficacy of policosanol was that expected. These results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure; SAE were not more frequent in the policosanol group than in the placebo group and there was no increase in AE.

Adrenergic beta-Antagonists↗

Early elimination of cyclosporine in kidney transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions.

Cyclosporine elimination in a regimen including sirolimus has been shown to be a safe and effective approach to improve graft function. Nevertheless, it is still unknown whether the functional benefit of CyA withdrawal coincides with a subsequent reduction in histologic lesions of chronic damage or development of chronic allograft nephropathy. This consideration would forecast a reduction in the rate of long-term graft loss. We analyzed 114 graft biopsies from a subgroup of 57 patients that had been included in a randomized study to eliminate CyA at 3 months posttransplant from a regimen including sirolimus either in group A CyA + SRL vs group B of SRL with CyA elimination at 3 months. Every patient had two biopsies, one at transplantation and another at 1 year. The biopsy reading was performed in a blinded manner by a central pathologist using the Banff 1997 and the CADI classifications. A significantly lower rate of progression of tubular and interstitial chronic lesions between basal and 1-year biopsies was observed for group B patients. In addition, the incidence of new cases of chronic allograft nephropathy during the first year was significantly lower in the group in which CyA had been eliminated at 3 months posttransplant. We conclude that early elimination of CyA in the first months posttransplant, when SRL is used as the main immunosuppressant, reduces the appearance or worsening of chronic histologic lesions, probably as a consequence of long-term CyA toxicity prevention.

Biopsy↗

Identification of a differentially expressed mRNA in axenic Leishmania panamensis amastigotes.

Differential display technique was applied in order to identify transcripts which are present in axenic amastigotes but not in promastigotes of the Leishmania panamensis parasites. One of them was cloned and the sequence reveals an open reading frame of 364 amino acids (approximately 40 kDa). The deduced protein is homologous to the serine/threonine protein kinases and specially to the mitogen activates protein kinases from eukaryotic species. Southern blot analysis suggest that this transcript, named lpmkh, is present in the genome of the parasite as a single copy gene. These results could imply that lpmkh could be involved in the differentiation process or the preservation of amastigotes in axenic conditions.

Amino Acid Sequence↗

Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma.

Glioblastoma multiforme (GBM) tumors display extensive histomorphological heterogeneity, with great variability in the extent of invasiveness, angiogenesis, and necrosis. The identification of genes associated with these phenotypes should further the molecular characterization, permitting better definition of glioma subsets that may ultimately lead to better treatment strategies. Therefore, we performed a differential mRNA display analysis comparing six GBM-derived primary cell cultures from patients having tumors with varied histomorphological features. We identified stromal cell-derived factor 1 (SDF1) as a gene with varied expression. SDF1 (cytokine) and CXC chemokine receptor 4 (CXCR4) interactions are implicated in modulating cell migration. They are also implicated in modulating the immune response in AIDS patients by macrophage-mediated T-cell apoptosis. GBM patients also fail to mount an immune response, although their tumors are seemingly exposed to immune cells in regions of angiogenesis, where the blood-brain barrier is absent, or in areas of necrosis. To determine whether the expression and localization of SDF1 and CXCR4 are consistent with such a role in these brain tumors, immunohistochemical analyses of these proteins were performed on normal brain and astrocytomas (grades II-IV). In normal brain tissue, low levels of SDF1 (0.5+) were observed in astrocytic processes, in neurons, and in the occasional phagocytic cells around vessels. CXCR4 expression was negative in brain tissue but was observed in phagocytic cells within the vessel lumen. In tumors, SDF1 and CXCR4 expression was colocalized when both were expressed, and SDF1 and CXCR4 expression increased with increasing tumor grade (from 0.5+ to 6+). Additionally, CXCR4 was expressed in neovessel endothelial cells. The proteins were expressed in regions of angiogenesis and degenerative, necrotic, and microcystic changes. Those tumors displaying greater amounts of these features had greater staining intensity of the proteins. The expression of SDF1 and CXCR4 did not colocalize with the proliferation marker MIB-1. Thus, our data suggest that SDF1 and CXCR4 expressions: (a) increase with increasing grade; (b) colocalize to regions within these tumors where their interaction may contribute to angiogenesis and/or modulation of the immune response; and (c) may serve to characterize subsets of GBMs.

Astrocytoma↗

SPARC: a potential diagnostic marker of invasive meningiomas.

SPARC, a secreted, extracellular matrix-associated protein implicated in the modulation of cell adhesion and migration, was evaluated as a marker for invasive meningiomas. Although the majority of meningiomas are clinically and morphologically benign, approximately 10% progress into atypical and malignant tumors, according to the standard criteria. However, a subset of meningiomas presents as histomorphologically benign tumors (WHO grade I), but they are clinically invasive. It has been suggested that these tumors should be classified as malignant, and that the patients may require adjuvant therapy and closer follow up. Unfortunately, a significant number of these tumors may not be recognized because the surgical specimen used to assess the grade of a tumor lacks the infiltrative interface with the brain, which is currently necessary to determine its invasive character. Therefore, a marker of heightened invasiveness would greatly facilitate the identification of this subset of patients. In this study, the immunohistochemical expression of SPARC in benign, noninvasive primary meningiomas was compared with its expression in invasive, aggressive, primary and recurrent meningiomas. SPARC was not expressed in the 9 benign, noninvasive tumors, but was highly expressed in the 20 invasive tumors, regardless of the grade. The findings suggest that SPARC is a potential diagnostic marker of invasive meningiomas and is capable of distinguishing the histomorphologically benign noninvasive from the histomorphologically benign but invasive meningiomas, in the absence of the infiltrative interface.

Biomarkers, Tumor↗

SPARC: a signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas.

In an attempt to identify genetic alterations occurring early in astrocytoma progression, we performed subtractive hybridization between astrocytoma and glioblastoma cDNA libraries. We identified secreted protein acidic and rich in cysteine (SPARC), a protein implicated in cell-matrix interactions, as a gene overexpressed early in progression. Northern blot and immunohistochemical analyses indicated that transcript and protein were both elevated in all tumor specimens (grades II-IV) examined when compared with levels in normal brain. The level of SPARC expression was found to be tumor-dependent rather than grade-related. Immunohistochemically, SPARC protein was found to be overexpressed in 1) cells in the less cellularly dense regions within the tumor mass, 2) histomorphologically neoplastic-looking cells in adjacent normal brain at the tumor/brain interface, 3) neovessel endothelial cells in both the tumor and adjacent normal brain, and 4) reactive astrocytes in normal brain adjacent to tumor. Using a combination of DNA in situ hybridization and protein immunohistochemical analyses of the human/rat xenograft, SPARC expression was observed in the human glioma cells within the tumor mass, and in cells that invaded along vascular basement membranes and individually into the rat brain parenchyma, suggesting it may be an invasion-related gene. While it remains to be determined whether SPARC functionally contributes to tumor cell invasion, these data suggest that the early onset of increased SPARC expression, though complex, may serve as a signal indicative of neoplastic astrocytic transformation and reactive response to tumor-induced stress.

Animals↗

Organ-preserving management of rhabdomyosarcoma of the prostate and bladder in children.

Between November 1978 and July 1991, ten children between one and eight years of age with Group III pelvic rhabdomyosarcoma (IRS classification) and considered inoperable at diagnosis were treated primarily with intensive poly-chemotherapy. Complementary radiotherapy and conservative surgery were added as needed. Eight of the ten survive free of disease with functioning bladders for periods ranging from 5.7-18.4 years.

Antineoplastic Combined Chemotherapy Protocols↗

[Nutritional status of preschool children in Ciudad de La Habana from 1972 to 1993].

Two anthropometric surveys of children and adolescents have been carried out in Cuba with national samples. A third study done in the province of Ciudad de la Habana provided information on the physical characteristics of the population in that area and a baseline for the periodic evaluation of its nutritional status. This article compares the weight and height results obtained in these surveys for children 0 to 5 years old who lived in this province with the international reference standards proposed by WHO. The results show that, despite the economic difficulties the country has faced, the prevalence of malnutrition is low. In 1993, the prevalence of low height-for-age was 3.1%; that of low weight-for-height, 0.4%; and that of low weight-for-age, 1.5%. Overweight was the most common type of malnutrition, with a prevalence of 5.2%. Between 1972 and 1993, the prevalence of chronic malnutrition fell 32.6%, acute malnutrition was reduced by 69.2%; malnutrition of all types decreased by 44.4%; and overweight fell 48.5%.

Anthropometry↗

Hemodynamic effects of high-frequency oscillatory ventilation in severe pediatric respiratory failure.

OBJECTIVE: To assess the hemodynamic effects of high mean proximal airway pressures (Paw) during high-frequency oscillatory ventilation (HFOV) in non-neonatal pediatrics patients with severe respiratory failure. DESIGN: Prospective and retrospective study. SETTING: Pediatric ICU in a university-affiliated hospital. PATIENTS: 8 non-neonatal pediatric patients with severe respiratory failure ventilated with HFOV at our institution between July 1991 and February 1994. All patients had a pulmonary artery catheter. INTERVENTIONS: HFOV. MEASUREMENTS AND RESULTS: Higher Paw was required during HFOV to obtain adequate lung expansion during the first 24 h (median 20.9 cmH2O, range 16.9-30.0 cmH2O in CMV, versus median 30.0 cmH2O, range 21.0-33.0 cmH2O in HFOV, p = 0.008), resulting in improved oxygenation as evaluated by alveolar-arterial oxygen difference (median of 557.2 mmHg, range 360.4-607.8 mmHg in CMV, versus median of 410.5 mmHg, range 282.9-550.2 mmHg after 24 h of HFOV, p = 0.03). The only observed effect on the cardiovascular system was a decrease in heart rate (median of 162, range 129-178 in CMV, versus median of 142, range 104-195 after 24 h of HFOV, p = 0.03). Oxygen delivery, cardiac index, mean systemic arterial blood pressure, and pulmonary and systemic vascular resistances did not change significantly before and after HFOV in the patients as a group, although in one case a decrease in cardiac index and oxygen delivery was observed. CONCLUSIONS: High-Paw HFOV must be used cautiously, but seems to have no discernible adverse effects on the cardiovascular system in most patients.

Analysis of Variance↗

Commissural dehiscence of Carpentier-Edwards mitral bioprostheses. Explant analysis and pathogenesis.

Manufacturing factors have seldom been implicated as a direct cause of structural deterioration of valvular bioprostheses; this phenomenon has generally been considered to be of a host-dependent origin. We analyzed the clinical and pathologic data from 12 Carpentier-Edwards mitral bioprostheses removed from 12 patients because of severe dysfunction and showing detachment of the porcine aortic wall from the stent in one commissure or more. These 12 prostheses were part of a group of 92 such valves that were explanted and displayed structural deterioration. They belong to a population of 405 Carpentier-Edwards bioprostheses implanted in the mitral position in our institution between May 1978 and November 1988. The patients included three men and nine women with a mean age of 54 +/- 13 years. One patient had a history of chronic renal failure, and two had systemic hypertension. Prosthesis sizes were 29, 31, and 33 mm (n = 4 for each size). The models of the valves were 6625 (n = 8) and 6650 (n = 4). Mean duration of implantation of the prostheses was 99 +/- 27 months (52 to 136 months) and did not differ depending on the model. There was no significant clustering of commissural detachments depending on valve size, year of implantation, or gender of the patient. No similar phenomenon was observed among 76 explanted aortic Carpentier-Edwards bioprostheses with structural deterioration from a population of 441 valves implanted during the same time frame. Native porcine aortic roots (n = 5) and aortic Carpentier-Edwards bioprostheses explanted because of structural deterioration (n = 4) were used as controls for comparison. Macroscopic examination showed single commissural dehiscence in 10 patients and double in two. Radiology disclosed no or mild mineralization in eight valves and no calcium in the area of aortic wall dehiscence, except for heavily calcified valves. Light microscopy evidenced a significant thinning of the aortic wall at the paracommissural level of mitral bioprostheses (351 +/- 68 microns) compared with either aortic bioprostheses (526 +/- 59 microns; p < 0.01) or control native porcine aortic roots (419 +/- 50 microns; p < 0.01). No difference was found in terms of aortic wall thickness between detached (322 +/- 42 microns) and intact (366 +/- 74 microns) commissures in mitral bioprostheses.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories).

We studied the influence of administration route on the biopharmaceutical behavior of etodolac. The levels obtained in plasma when the same dose of etodolac is administered orally (tablets, dosage form A) and rectally (suppositories, dosage form B) were compared. The study was done in a crossover design with healthy volunteers of both sexes, of average build, and younger than 35 years of age. From the concentration in plasma-time data, the maximum concentration in plasma (Cmax), time to Cmax, and area under the curve up to the last measurable concentration (AUC0t) or infinity (AUC 0 infinity) were calculated and compared by analysis of variance. With the exception of Cmax, no significant differences between treatments were found in the rest of the parameters. Finally, with formulation A (tablets) as a reference, the relative bioavailability was established, on the basis of the ratio (B:A) of AUC0t and AUC 9 infinity, within the range 100 +/- 20%. The results indicate that the two routes of administration are bioequivalent and that the rectal route is an alternative administration route for etodolac.

Adolescent↗

[Changes in the lipid profiles of hyperlipemic patients treated with binifibrate].

Forty six, after six weeks of low fat diet (step 1) hyperlipidemic patients, age 20 to 65 years, both sexes, have been studied to recognize the effectiveness of three months drug treatment with Binifibrate (600 mg T.I.D.). Total cholesterol, triglycerides, LDL-cholesterol (cLDL), HDL-cholesterol (cHDL), apoprotein A, apoprotein B and other routinal biochemical parameters were controlled at 0, 30 and 60 days of treatment. A significative total cholesterol, cLDL and apo B lowering plus a significative cHDL and apo A increase was registered. Results reflect a beneficial effect of Binifibrate on lipoprotein metabolism and in such wise, locate this drug as an interesting one for hyperlipidemic situations treatment.

Adult↗