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Biomedical subjects

A Ortega

Publications and source records attributed to A Ortega.

At least 91 records · Page 5Linked to original sources

Presence of a nitric oxide synthase inhibitor in the graft efflux during reperfusion in human liver transplantation.

Involvement of the nitric oxide (NO) system in complications following human orthotopic liver transplants (OLT) has been reported, but the contribution of the graft to the modulation of the NO system during reperfusion in normal OLT has not been characterized. We have studied the contribution of the graft efflux to the modulation of the NO system in 20 consecutive OLT. We evaluated its effects on isolated vascular reactivity of the rabbit and on rat cultured macrophages stimulated with lipopolysaccharide (LPS). In none of the donor liver biopsies was expression of inducible NO synthase (iNOS) activity by Northern or Western blot analysis found. Graft efflux after the onset of liver reperfusion, but not pre-transplant patient plasma, reversibly inhibited the acetylcholine-induced relaxation of norepinephrine-contracted rabbit aortic rings. Moreover, graft efflux reversibly inhibited NO production in rat macrophages treated with LPS, as evidenced by both a decrease in nitrite plus nitrate formation and a decrease in the production of [14C]citrulline from [14C]arginine. Addition of a 10% dilution of graft efflux to cultured rat macrophages incubated with LPS increased iNOS mRNA levels, suggesting direct inhibition of the enzyme but not of its expression. These results cannot be ascribed to the depletion of arginine the iNOS substrate since they can be reproduced even in the presence of an excess (10 mM) of exogenously added arginine. No correlation was found between the iNOS inhibitory activity in each sample and the corresponding clinical parameters related to either the graft function after the OLT or the existence of post-reperfusion syndrome. Our results indicate the existence of a soluble factor in the graft efflux from human OLT that reversibly and unspecifically inhibits NOS activity. Its involvement in the physiology and/or pathology of human liver diseases deserves further study.

Acetylcholine↗

Mycobacterium tuberculosis subsp. caprae subsp. nov.: a taxonomic study of a new member of the Mycobacterium tuberculosis complex isolated from goats in Spain.

Isolates from the Mycobacterium tuberculosis complex cultured from caprine pathological tissue samples were biochemically and genetically characterized. The isolates were negative for nitrate reduction and niacin accumulation, they weakly hydrolysed Tween 80, were sensitive to pyrazinamide (50 micrograms ml-1) and were resistant to 1 and 2 micrograms tiophene-2-carboxylic acid hydrazide ml-1 but not to 5 or 10 micrograms tiophene-2-carboxylic acid hydrazide ml-1. Sequencing of the pncA gene revealed a polymorphism characteristic of M. tuberculosis, whereas oxyR, katG and gyrA sequences were characteristic of Mycobacterium bovis. The fingerprinting patterns obtained with IS6110, direct repeats and polymorphic G+C-rich sequence-associated RFLP and direct variable repeat-spacer oligonucelotide typing (spoligotyping) segregated these isolates from the other members of the complex. The results of this testing, together with the repeated association of this micro-organism with goats, suggest that a new member of this taxonomic complex not matching any of the classical species had been identified. This unusual mycobacterium may play a role in the epidemiology of animal and human tuberculosis in Spain. The name Mycobacterium tuberculosis subsp. caprae subsp. nov. is proposed for these isolates. The type strain of Mycobacterium tuberculosis subsp. caprae subsp. nov. is gM-1T (= CIP 105776T).

Amidohydrolases↗

[Tox-Didact:CD-ROM for toxicology education. Value in hospital toxicology].

New teaching techniques should allow students more independence in their training, particularly in learning from problems and using clinical reasoning. We designed Tox-Didact, a modular multimedia educational software program, which is suitable for both students and professionals, regardless of their orientation (pharmacy or medicine) or level. Each module concerns four domains: diagnosis, biological monitoring, curative treatment and prevention. Tox-Didact is multidisciplinary, interactive, simple to use and reliable. Nineteen modules are now being prepared. In final form, Tox-Didact will cover all the acute and chronic pathologies of toxicology.

CD-ROM↗

[Scintigraphy diagnosis of renovascular hypertension in renal transplanted patients].

UNLABELLED: Captopril renography (CR) has been shown to be a useful technique in the diagnosis of renovascular hypertension (RVH). This disease is a significant complication of the kidney transplanted patient so that early diagnosis would be extremely useful to preserve renal function and prevent graft loss. This work evaluates the role of CR, together with arteriography and doppler-ultrasound, in the diagnosis of RVH. MATERIALS: A total of 19 transplanted patients with clinical suspicion of RVH underwent an isotopic study, a doppler-ultrasound study and an arteriography. Scintigraphy was performed 1 hour after a 50 mg dose of captopril, with oral hydration and i.v. administration of approximately 111 MBq of 99mTc-MAG3 and 20 mg of furosemide. If abnormal, a subsequent renography in baseline conditions was performed for comparison. RESULTS: Overall, 11 patients had renovascular hypertension. Sensitivity and specificity of CR were 91% and 80% respectively, 100% and 60% for US and 91% and 100% for arteriography. The CR yielded one false positive result and 2 false negatives cases: one with 50% stenosis and one polar artery stenosis. Six patients were successfully dilated or operated. CONCLUSION: CR seems to be a reliable diagnostic tool for the diagnosis of renovascular hypertension in kidney transplanted patients.

Adult↗

What are cancer patients willing to pay for prophylactic epoetin alfa? A cost-benefit analysis.

BACKGROUND: Anemia, one of the most common complications of cancer chemotherapy, has been managed with red blood cell (RBC) transfusions. As an alternative, the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy. To estimate the value that cancer patients place on the drug, an economic analysis using the concept of willingness to pay (WTP) was conducted. METHODS: The method of WTP was used within the framework of a classical cost-benefit analysis to estimate the net cost or benefit of administering prophylactic epoetin alfa to cancer patients. This estimate included the direct cost of epoetin alfa administration and savings secondary to reduced RBC transfusions. A cohort of 100 cancer patients who received or were scheduled to receive cisplatin or noncisplatin chemotherapy (50 per group) were then interviewed to measure the maximum WTP (net benefit) that they experienced with epoetin alfa. RESULTS: Regarding the benefits they would experience after 3 months of epoetin alfa administration, patients receiving cisplatin and noncisplatin therapy stated that they would be willing to pay an average of 587 U.S. dollars (U.S.$587) (95%CI: $300-$875) and U.S.$613 (95%CI: $324-$902), respectively. These benefits were then subtracted from the total cost of the drug when administered to patients receiving cisplatin (U.S.$3530) and noncisplatin (U.S.$3653) therapy. This produced a net incremental treatment cost of U.S.$2943 (95%CI: $2655-$3230) and U.S.$3039 (95%CI: $2750-$3328) for the respective treatment groups. CONCLUSIONS: The results of the current study suggest that the routine administration of epoetin alfa to cancer patients receiving myelosuppressive chemotherapy is a highly resource-intensive treatment policy with modest benefit to patients. Additional research is required to identify high risk patient subgroups who would benefit most from the drug. [See editorial on pages 2427-9, this issue.]

Anemia↗

Putative dengue virus receptors from mosquito cells.

Dengue viruses are arthropod-borne, single-stranded RNA viruses. Aëdes aegypti and Aëdes albopictus are the principal vectors. In order to understand the molecular basis of dengue virus infections we explored the biochemical identity of dengue-2 (DEN-2) virus receptors in the Aëdes albopictus-derived cell line C6/36. We show here that DEN-2 interacts with two major polypeptides of 80 and 67 kDa. Polyclonal anti-C6/36 membrane antibodies block DEN-2 binding to intact C6/36 monolayers as well as to membrane extracts. Our results strongly suggest that the identified polypeptides are part of the DEN-2 receptors.

Aedes↗

Determinants of a positive exercise test in patients admitted with acute non-infarct chest pain.

BACKGROUND AND OBJECTIVES: Some patients with suspected unstable angina show ischemia at the exercise treadmill test despite having been medically stabilized. The objective of this study was to determine clinical characteristics predicting a positive exercise treadmill test in patients with suspected unstable angina after medical stabilization. METHODS: In 885 hospitalized patients with medically stabilized unstable angina, the relationship between the result of the pre-discharge exercise treadmill test and clinical characteristics was studied. RESULTS: Mean age was 62+/-9 years and 668 (75%) were male. Exercise test was positive (chest pain and/or ST depression > or =1 mm) in 288 patients (33%). Univariate analysis showed the following associated with ischemia at the exercise test: male gender (56% vs. 20%, P<0.001 ), diabetes mellitus (41% vs. 31%, P=0.009), previous unstable angina (41% vs. 24%, P=0.001), previous stable angina (44% vs. 30%, P<0.001), previous coronary artery bypass grafting (43% vs. 31%, P=0.043), peripheral artery disease (45% vs. 31%) and progressive angina (55% vs. 31%, P<0.001). Multivariate analysis showed the following as independent predictors of ischemia: male gender (OR=2.25), diabetes (OR=4.12), previous unstable angina (OR=3.89), previous stable angina (OR=3.74) and progressive angina (OR=4.05). CONCLUSIONS: In patients with suspected unstable angina, after medical stabilization: (1) the exercise treadmill test is positive in one-third of cases; (2) male gender, diabetes, previous angina (unstable and stable) and progressive angina are independent predictors of ischemia.

Acute Disease↗

Changes in GluR4 expression induced by metabotropic receptor activation in radial glia cultures.

The expression of neurotransmitter receptors in glial cells has suggested a regulatory role of these cells in synaptic function. In radial glia, glutamate receptors elicit a cascade from the membrane to the nucleus and a consequent change in gene expression. In order to gain insight into this process, we address the question of whether receptor activation leads to changes in the repertoire of AMPA/KA glutamate receptor subunits in Bergmann and Müller glial cells. Of the subunits investigated, only GluR4 was up-regulated in Bergmann glial cells both at mRNA and protein levels. In contrast, in Müller glial cells Glu treatment leads to a reduction in GluR4 mRNA and protein expression. Both effects are receptor-mediated and must probably involve group I of metabotropic glutamate receptors. Accordingly, using Northern blot analysis and RT-PCR we detected the expression of both mGluR1 and mGluR5 transcripts in the cultured cells. Our results confirm that glutamate receptors in Bergmann and Müller cells modulate gene expression and further strengthen a plausible role of glial cells in long-lasting changes in the central nervous system.

Animals↗

Predictors of multivessel disease in cases of acute chest pain.

BACKGROUND: Patients with unstable angina not showing ischemia at the exercise treadmill test after medical stabilization usually have a low-risk coronary anatomy. However, some of them have multivessel disease, and it is not known what characteristics are associated with the extension of the coronary artery disease in this subset of patients. OBJECTIVE: To determine clinical and exertional characteristics associated with multivessel disease in patients with unstable angina and a negative exercise test. METHODS: 312 hospitalised patients with unstable angina and a negative exercise test who had undergone cardiac catheterization were reviewed. The relationship between coronariographic findings (presence of multivessel disease) and clinical characteristics, exercise parameters and left ventricular function was studied. RESULTS: Multivessel disease was present in 97 patients (31%). The following variables were associated with the presence of multivessel disease: age more than 65 years old, previous myocardial infarction, previous admissions because of unstable angina, peripheral artery disease, presence of more than two coronary risk factors, left ventricular dysfunction, functional capacity less than 6 METS, duration of exercise less than 8 min and less than 85% of the maximum heart rate. Multivariate analysis showed, as independent predictors of multivessel disease: previous myocardial infarction, previous admissions because of unstable angina, presence of more than two coronary risk factors and peripheral artery disease. CONCLUSIONS: In patients with medically stabilized unstable angina and a negative exercise test, previous myocardial infarction, previous admissions because of unstable angina, presence of more than two coronary risk factors and peripheral artery disease, but not exercise parameters, are independent predictors of multivessel disease.

Aged↗

Entamoeba histolytica: collagen-induced AP-1 DNA binding activity.

The interaction of Entamoeba histolytica trophozoites with collagen induces the synthesis and release of electron-dense granules containing a collagenase activity that is an important factor in the pathogenicity of the parasite. The binding is thought to be mediated by an 'integrin-like' collagen receptor. In the signal transduction mechanisms activated by collagen, pp125FAK and p42MAPK are involved. Using immunoprecipitation assays coupled to Western blot analysis, we demonstrate here the collagen-dependent association of paxillin and Src with pp125FAK. Furthermore, collagen induces a time-dependent increase in the DNA binding activity of the activator protein 1, which is well correlated with an increase in Fos expression. Our results suggest that a stimulus-transcription coupling triggered by collagen in E. histolytica trophozoites might activate or repress genes involved in tissue invasiveness.

Animals↗

Abdominal incision tumor implantation following pneumoperitoneum laparoscopic procedure vs. standard open incision in a syngeneic rat model.

INTRODUCTION: A recent hamster model study suggests that the abdominal wall wound implantation rate increases following laparoscopic colon cancer surgery compared with the traditional open technique. However, results of that study were confounded by several factors, including a midline incision in the laparoscopy group, an unclear definition of wound implantation, significant age variations in study subjects, and cell line use with low viability. The aim of this study was to compare the abdominal incision implantation rates following a pneumoperitoneum-laparoscopic-type procedure with a standard open incision using a syngeneic host/colon cancer rat model. METHODS: Viable DHD/K12 rat colon carcinoma cells (2 x 10(5) cells/rat) were injected intraperitoneally via 18G angiocath into anesthetized, immunocompetent BD-IX rats (syngeneic host rats). Rats were then randomly divided into open incision and laparoscopy groups. At three weeks post-operatively, tumor growth at the injection, incision, and port sites was measured. RESULTS: Following standard midline incision, 50 percent of rats (26/50 rats) developed wound implantations, whereas only 25 percent of rats (14/57 rats) developed at least one trocar site wound implantation after laparoscopy with pneumoperitoneum. Fourteen percent of trocar sites (16/114 port sites) developed wound implantations. No tumor growth was noted on the peritoneal surfaces other than in the incisional sites. CONCLUSION: Laparoscopic-type procedure with pneumoperitoneum did not increase wound implantation in a syngeneic host/colon carcinoma rat model compared with the standard open incision technique.

Abdominal Muscles↗

Urinary levels of metallothioneins and metals in subjects from a semiindustrialized area in Tarragona Province of Spain.

The monitoring of heavy metals is important if adverse effects on health are to be avoided. In humans, metallothionein (MT) has been used as a biomonitor for the assessment of cadmium (Cd). In the present study, subjects drawn from the population of Tarragona Province (NE Spain) were investigated. Urinary MT, zinc (Zn), and copper (Cu) concentrations, corrected for creatine concentrations, were determined in 625 samples from healthy subjects aged between 10 and 65 yr. Mean values of MT and Cu in females were higher than those in males, with levels of 29.5 (23.8) vs. 22.7 (24.9) micrograms MT/creatinine (p < 0.001) and 4.8 (6.1) vs 3.4 (4.9) micrograms Cu/g creatinine (p < 0.001). No differences between males and females were observed with respect to urinary Zn: 78.0 (66.4) vs 73.0 (85.5) micrograms/g creatinine, respectively (p = 0.332). Significantly higher MT, Zn, and Cu values were observed in the females aged 15-19 yr and, in the age group of 50-54 yr, only in the Zn and Cu values, when compared with those in males. Significant positive correlations of MT vs Zn and Cu as well as correlations of Zn vs Cu levels were observed in both genders. The present findings confirm the proposed role of MT as a biomonitor of mineral status.

Adolescent↗

A clinical and economic evaluation of red blood cell transfusions in patients receiving cancer chemotherapy.

A clinical and economic evaluation of red blood cell (RBC) utilization in cancer patients during chemotherapy is described. Using a randomized sampling process, 100 patients who had received chemotherapy with or without cisplatin were selected (50 in each group). Multiple logistic regression was then used to identify risks factors for transfusion requirements. Twenty-five percent of patients in the cisplatin and 12% in the noncisplatin group received at least one blood transfusion during chemotherapy (p = .09). Depressed hemoglobin levels and cisplatin dosage were identified as risk factors for transfusion requirements. Combining all transfused patients revealed an overall cost of Can $599 (95% CI: $513-$683) per transfusion. The results of the current study indicated that anemia is a common complication of cancer chemotherapy that can be costly to manage.

Anemia↗

Galphimine-B modifies electrical activity of ventral tegmental area neurons in rats.

Galphimine-B (G-B) is a bioactive compound isolated from the plant Galphimia glauca Cav. (Malpighiaceae) with central nervous system depressant properties previously described. In the present study, extracellular spiking activity records in either somatosensorial cortex or ventral tegmental area (VTA) neurons, were performed in rats after i.p. or local administration of G-B. None of the cortical neurons displayed significant changes induced by any of the applied doses. In VTA cells, two patterns of electrical discharge were recorded, bursting (57%) and nonbursting (43%) types. Systemic administration of G-B induced excitatory effects in neurons with a bursting firing pattern and mixed responses on nonbursting units. When this compound was applied locally by microiontophoresis, most of the bursting and nonbursting spiking neurons showed a firing depression and only a few of the nonbursting neurons showed an increment of discharge frequency. These results are important since VTA is a major dopaminergic center responsible for the innervation of the prefrontal cortex, nucleus accumbens and entorhinal region. These areas are targets for the action of antipsychotic drugs.

Action Potentials↗

Population pharmacokinetic parameters of gentamicin in patients with solid tumors: estimation by one- and two-stage methods.

Gentamicin monitoring has been improved with the introduction of Bayesian methods but the usefulness depends on the quality of the population parameters (PP) used. The objective of this study was to determine PP of gentamicin in patients with solid tumors. A total of 198 adult patients with cancer were included in the analysis. Population parameters were estimated by both a two-stage and a one-stage method (NPEM, Non Parametric Expectation Maximization). Individual parameters (IP) were estimated by the Sawchuk-Zaske method and by nonlinear regression. The estimated distribution volume and clearance of gentamicin (mean +/- SD) were 18.37 +/- 5.021 (0.30-0.32 l/kg of dosing weight) and 3.34 +/- 1.6 l/h, respectively. No significant differences between IP or PP obtained by the different methods were found. The results indicated a wide variability of gentamicin pharmacokinetics making monitoring necessary and that patients with solid tumors may have larger gentamicin volume and slower clearance than normal patients. These observations imply that different population pharmacokinetic parameters should be used for this group of patients.

Adult↗

The post-larval development of lateral musculature in gilthead sea bream Sparus aurata (L.) and sea bass Dicentrarchus labrax (L.).

Fibre-type differentiation of lateral musculature has been studied in gilthead sea bream Sparus aurata (L.) and sea bass Dicentrarchus labrax (L.) during post-larval development using ultrastructural, histochemical and morphometric techniques. The study showed three muscle layers: red, intermediate (or pink) and white. Initially, most of the red muscle showed low myosin ATPase (m-ATPase) activity fibres, whereas near the transverse septum some small high m-ATPase activity fibres appeared and later acquired a rosette aspect. Afterwards, during adult growth the red muscle showed a histochemical mosaic appearance. The pink muscle in sea bass was observed at the beginning of juvenile development by the oxidative technique (NADH-RT reaction) whereas in gilthead sea bream it was also observed at the end of larval development. The pink layer consists of high m-ATPase activity fibres. However, along the muscle development other low and moderate m-ATPase activity fibres were observed close to the red and white muscles, respectively. The white muscle of juvenile fish showed a histochemical mosaic appearance near the pink muscle. In adult specimens the mosaic white muscle spread out occupying the whole of the myotome. Morphometric analysis shows a significant increase in mean fibre diameter during post-larval development, as shown by the Student's t-test (hypertrophic growth). Skewness and kurtosis values of fibre diameters point to the generation of a new fibres from the myosatellite cells (hyperplastic growth).

Animals↗