Biomedical subjects

A Ortega

Publications and source records attributed to A Ortega.

At least 73 records · Page 4Linked to original sources

PubMed2000

Clinical and economic impact of a pharmacist-intervention to promote sequential intravenous to oral clindamycin conversion.

A multicentre, prospective, controlled study compared the clinical efficacy, safety and economic impact of a pharmacist intervention to promote sequential intravenous to oral clindamycin conversion. A total of 473 patients receiving intravenous clindamycin for at least 72 hours were included in the study. Two groups were established: an intervention group (204 patients) in which an informative sheet recommending the sequential treatment was provided, and a control group (269 patients). Clindamycin was prescribed for respiratory infections in 38.9% and for prophylaxis in surgery in 25.4% of the patients (71% were contaminated surgery). No difference between groups regarding sex, infection severity, health status or clinical progress was observed. Both the step-down treatments after 72 hours of intravenous clindamycin and the change to the oral route later on, were significantly increased with the intervention (p < 0.001, p < 0.001 respectively). No significant differences between both groups were found in the number of patients with adverse effects associated with the i.v. therapy, although the incidence tended to be lower in the intervention group (49/204 intervention versus 85/269 control, p = 0.07). Compliance with the recommended clindamycin dosing regimen was significantly higher in the intervention group, in which 1.3 days reduction of intravenous therapy provided an average cost savings of PTA5246 (95% CI 2556-7935) per treatment. A higher reduction of 1.7 days was achieved in those patients candidates for switch therapy on the third day of intravenous clindamycin. A sequential program with clindamycin may provide a cost-effective alternative to conventional therapy and the introduction of an information sheet is a cost-effective strategy to promote it.

Administration, Oral↗

PubMed2000

Transanal versus open endorectal pull-through for Hirschsprung's disease.

PURPOSE: Transanal endorectal resection and pull-through technique (TERPT) for Hirschsprung's disease (HD) was described in 1998. It offers the advantages of avoiding laparotomy, laparoscopy, scars, abdominal contamination, and adhesions. The authors compared TERPT with 2 open standard endorectal pull-through approaches. METHODS: Twenty-eight HD patients operated on by endorectal pull-through were compared in 3 groups. Group I had 10 patients with preliminary colostomy approached by laparotomy; group II, 8 by laparotomy; and group III, 10 patients treated by TERPT. Age, operating time and bleeding, complications, follow-up, and functional results were analyzed. Mean, standard deviation, and median were calculated. Groups were compared by 1-way analysis of variance (ANOVA) using the Kruskal-Wallis test. RESULTS: Age and length of follow-up were not statistically different (P = .12 and .07, respectively). Operating time and bleeding were less in group III (P = .03 for both). An intestinal obstruction secondary to adhesions and a subhepatic abscess occurred in group I and II, respectively. Minimal complications occurred in group III. Good functional results were obtained in 80% to 90% of the patients in all groups. CONCLUSION: TERPT minimizes blood loss in this study, was expeditious, uncomplicated, and as effective as the open standard techniques.

Anal Canal↗

PubMed2000

Abdominal insufflation does not cause hematogenous spread of colon cancer.

BACKGROUND AND PURPOSE: Previous investigators have suggested that port-site recurrences are possibly a result of abdominal insufflation, forcing viable cancer cells into the circulation to metastasize and thrive in areas of trauma. Using a syngeneic animal cancer model, we tested the hypothesis that pneumoperitoneum increases the incidence of wound metastasis by a blood-borne mechanism. METHODS: Male BD IX rats (N = 150) were injected intraperitoneally with 2 x 10(5) viable syngeneic 1,2-dimethylhydralazine-induced colon cancer cells (DHD-K12). Animals were divided into three groups: A (abdominal insufflation with 3-cm incision on the back into muscle remote from the peritoneum); B (3-cm back incision alone); and C (control group with 3-cm midline abdominal incision). Three weeks after surgery, the animals were euthanized and autopsied. RESULTS: In the two groups with back wounds, the incidence of cancer growth at the incision was zero, as demonstrated grossly and by histologic sample (A: 0/47, B: 0/43). In contrast, the autopsied control group had a 42% incidence of metastasis to the wound (25/59). There seemed to be no difference in the distribution of intra-abdominal disease between those rats that underwent insufflation and those that did not. CONCLUSION: It is unlikely that pneumoperitoneum promotes hematogenous wound implantation of free intraperitoneal cancer cells.

Animals↗

PubMed2000

The Drosophila fl(2)d gene, required for female-specific splicing of Sxl and tra pre-mRNAs, encodes a novel nuclear protein with a HQ-rich domain.

The Drosophila gene female-lethal(2)d [fl(2)d] interacts genetically with the master regulatory gene for sex determination, Sex-lethal. Both genes are required for the activation of female-specific patterns of alternative splicing on transformer and Sex-lethal pre-mRNAs. We have used P-element-mediated mutagenesis to identify the fl(2)d gene. The fl(2)d transcription unit generates two alternatively spliced mRNAs that can encode two protein isoforms differing at their amino terminus. The larger isoform contains a domain rich in histidine and glutamine but has no significant homology to proteins in databases. Several lines of evidence indicate that this protein is responsible for fl(2)d function. First, the P-element insertion that inactivates fl(2)d interrupts this ORF. Second, amino acid changes within this ORF have been identified in fl(2)d mutants, and the nature of the changes correlates with the severity of the mutations. Third, all of the phenotypes associated with fl(2)d mutations can be rescued by expression of this cDNA in transgenic flies. Fl(2)d protein can be detected in extracts from Drosophila cell lines, embryos, larvae, and adult animals, without apparent differences between sexes, as well as in adult ovaries. Consistent with a possible function in posttranscriptional regulation, Fl(2)d protein has nuclear localization and is enriched in nuclear extracts.

Alternative Splicing↗

PubMed2000

Effects of hepatic function on vancomycin pharmacokinetics in patients with cancer.

Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer. The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these patients. A population pharmacokinetic analysis was performed using the global two-stage method. To this purpose serum vancomycin concentrations from 154 cancer patients were measured and individual vancomycin pharmacokinetic parameters were estimated by the Sawchuk and Zaske method. Mean and standard deviation of the vancomycin pharmacokinetic parameters were estimated for various subgroups of patients classified according to the degree of liver damage. Then a multiple linear regression analysis was performed to select the best predictive models for vancomycin clearance (Clvan) and steady state distribution volume (V). Results revealed that Clvan is not influenced by liver failure. Differences in V between patients with and without hepatic failure were initially observed, but these disappeared when patients with ascites were excluded. In conclusion, vancomycin dosing schedule does not need to be modified for patients with liver failure, with the exception of patients with ascites.

Adolescent↗

PubMed2000

Evaluation of the MB/BacT mycobacterium detection system for susceptibility testing of Mycobacterium tuberculosis.

The MB/BacT mycobacterium detection system was evaluated for its performance in the susceptibility testing of Mycobacterium tuberculosis. Eighty-three M. tuberculosis isolates were processed. Results for all isoniazid-, rifampin- and streptomycin-susceptible, isoniazid-resistant, and rifampin-resistant M. tuberculosis isolates with the MB/BacT system agreed 100% with those obtained by the agar proportion method. The agreements between the two methods for streptomycin- and ethambutol-resistant isolates were 96.4 and 90.4%, respectively. The susceptibility test results were obtained in 7 days, on average. These data demonstrate that the MB/BacT system is an accurate, nonradiometric method for rapid susceptibility testing of M. tuberculosis.

Antimalarials↗

PubMed2000

Interaction of D-600 with the transmembrane domain of the sarcoplasmic reticulum Ca(2+)-ATPase.

Experiments were performed to determine whether the organic Ca(2+) channel blocker D-600 (gallopamil), which penetrates into muscle cells, affects sarcoplasmic reticulum (SR) Ca(2+) uptake by directly inhibiting the light SR Ca(2+)-ATPase. We have previously shown that at 10 microM, D-600 inhibits LSR ATP-dependent Ca(2+) uptake by 50% but has no effect on ATPase activity (21). These data suggest that the SR Ca(2+)-ATPase might be a potential target for D-600. The ATPase activity of the enzyme is associated with its hydrophilic cytoplasmic domain, whereas Ca(2+) binding and translocation are associated with the transmembrane domain (18). In the present experiments, we determined which of the two domains of the ATPase is affected by D-600. Thermal inactivation experiments using the SR Ca(2+)-ATPase demonstrated that D-600 decreased the thermal stability of Ca(2+) transport but had no effect on the stability of ATPase activity. In addition, D-600 at a concentration of 160 microM did not have any leaking effect of Ca(2+) on the Ca(2+)-loaded SR. Thermal denaturation profiles of SR membranes revealed that D-600 interacts directly with the transmembrane domain of the Ca(2+)-ATPase. No evidence for interaction with the nucleotide domain was obtained. We conclude that the Ca(2+) blocker D-600 inhibits the SR Ca(2+) pump specifically by interacting with the transmembrane Ca(2+)-binding domain of the Ca(2+)-ATPase.

Adenosine Triphosphatases↗

PubMed2000

Amino acid osmolytes in regulatory volume decrease and isovolumetric regulation in brain cells: contribution and mechanisms.

Brain adaptation to hyposmolarity is accomplished by loss of both electrolytes and organic osmolytes, including amino acids, polyalcohols and methylamines. In brain in vivo, the organic osmolytes account for about 35% of the total solute loss. This review focus on the role of amino acids in cell volume regulation, in conditions of sudden hyposmosis, when cells respond by active regulatory volume decrease (RVD) or after gradual exposure to hyposmotic solutions, a condition where cell volume remains unchanged, named isovolumetric regulation (IVR). The amino acid efflux pathway during RVD is passive and is similar in many respects to the volume-activated anion pathway. The molecular identity of this pathway is still unknown, but the anion exchanger and the phospholemman are good candidates in certain cells. The activation trigger of the osmosensitive amino acid pathway is unclear, but intracellular ionic strength seems to be critically involved. Tyrosine protein kinases markedly influence amino acid efflux during RVD and may play an important role in the transduction signaling cascades for osmosensitive amino acid fluxes. During IVR, amino acids, particularly taurine are promptly released with an efflux threshold markedly lower than that of K(+), emphasizing their contribution (possibly as well as of other organic osmolytes) vs inorganic ions, in the osmolarity range corresponding to physiopathological conditions. Amino acid efflux also occurs in response to isosmotic swelling as that associated with ischemia or trauma. Characterization of the pathway involved in this type of swelling is hampered by the fact that most osmolyte amino acids are also neuroactive amino acids and may be released in response to stimuli concurrent with swelling, such as depolarization or intracellular Ca(++) elevation.

Amino Acids↗

PubMed2000

Potential interaction between methotrexate and omeprazole.

OBJECTIVE: To report a case of delayed elimination of high-dose methotrexate (MTX) associated with concomitant omeprazole administration. CASE SUMMARY: Delayed MTX elimination was observed in an 11-year-old white boy who concomitantly received high-dose MTX and omeprazole. The patient's serum creatinine and liver function tests were normal during treatment and follow-up. The only medication we suspected of inhibiting MTX elimination was omeprazole 20 mg every 12 hours. Twenty-four hours after the first high-dose MTX cycle (15 g), omeprazole was discontinued. Thereafter, the patient received one high-dose MTX cycle without omeprazole every month for five months; MTX elimination was normal throughout MTX cycles 2 to 5. DISCUSSION: MTX is actively secreted in the distal tubules. The renal hydrogen/potassium adenosine triphosphatase (H+/K(+)-ATPase) pump makes the urine more acidic, by secreting hydrogen ions into the renal tubule and reabsorbing potassium ions. Active tubular secretion of MTX requires the activity of this pump because MTX is excreted with hydrogen ions. Omeprazole can inhibit renal elimination of the hydrogen ion and block the active tubular secretion of MTX. Therefore, the elimination half-life of MTX increases, which may result in potentially toxic concentrations of MTX. At a pH of approximately 5, as found in the renal tubules, pantoprazole is more slowly activated than omeprazole, reducing the incidence of unwanted reactions with sulfhydryl groups and adverse effects occurring outside of the gastric hydrogen pump. CONCLUSIONS: Based on the Naranjo probability scale, a probable drug interaction was observed. Omeprazole may delay MTX elimination; therefore, when prescribing MTX, an alternative to omeprazole should be considered.

Child↗

PubMed2000

[Usefulness of spect with 99mTc-tetrofosmin and stimulus with dipyridamole in patients with left bundle branch block of His].

BACKGROUND: In patients with left bundle branch block, the 201Tl scintigraphic studies show high sensitivity, but with low specificity, in the diagnosis of coronary artery disease. OBJECTIVE: [corrected] To assess the value of 99mTc-tetrofosmin Single Photon Emission Computed Tomography (SPECT) and dipyridamole administration in patients with left bundle branch block. METHODS: 22 patients with angina and left bundle branch block were retrospectively studied by cardiac catheterization and Tc-Tf after dipyridamole administration (0,142 mg/kg/min. i.v.) and at rest. RESULTS: The mean number of territories with perfusion defects was 1.5+/-1.0, and the average number of diseased vessels in the coronariographic study was 1.6+/-1.3 (r = 0.77, p<0.001). Sensitivity, specificity, positive predictive value, negative predictive value, total predictive value and Kappa index in the diagnosis of multivessel disease were 92%, 90%, 92%, 90%, 91% and 0.82, respectively. In the diagnosis of anterior descending artery disease, these values were 83%, 70%, 77%, 78%, 77%, and 0.54, respectively. CONCLUSION: In patients with angina and left bundle branch block, SPECT with Tc-Tf-dipyridamole is of great value in the study of coronary artery disease extension. Sensitivity and specificity for the diagnosis of anterior descending artery disease were similar to that shown in series with thallium-dipyridamole.

Bundle of His↗

PubMed2000

[Management of unstable angina: advanced age is still an independent predictive factor of more conservative management after prognostic stratification with stress test].

BACKGROUND AND OBJECTIVE: In the management of ischemic heart disease, elderly patients constitute a subgroup that, despite having a worse prognosis, are usually managed more conservatively. The objective of this study was to evaluate if, in the management of unstable angina, a more conservative attitude in elderly patients is maintained after stratification by exercise test. PATIENTS AND METHODS: The study population is constitude by 859 patients admitted to hospital due to suspected unstable angina that were referred to exercise test after medical stabilization. The management (invasive versus conservative, according to submission to cardiac catheterization or not) of patients was retrospectively studied, comparing patients < or = 70 versus > 70 years-of age. RESULTS: Out of the 859 patients, 156 (18%) were > 70 years old, and the exercise test was positive in 281 (33%). Cardiac catheterization was performed in 494 (57%): 62% in older and 38% in younger patients (p < 0.0001). Other characteristics associated with a more conservative management were: a negative exercise test, > 85% of the maximum heart rate, duration of exercise test more than 6 minutes, female gender, smoking and absence of episodes of rest angina. In the multivariate analysis, the statistically significant characteristics associated with an invasive management were the result of the exercise test (OR for positive result: 4.50; IC 95% = 2.73-7.63; p < 0.0001), the duration of exercise (OR for > or = 6 minutes: 0.51; IC 95% = 0.29-0.88; p = 0.0177), the percentage of the maximum heart rate (OR for > or = 85%: 0.65; IC 95% = 0.42-0.98; p = 0.0391) and age (OR for > 70 years 0.36; IC 95% = 0.20-0.62; p = 0.0004). CONCLUSIONS: In the management of unstable angina, elderly patients constitute a more conservatively managed subgroup even after risk stratification with exercise test.

Age Factors↗

PubMed1999

Alpha-adrenoceptor-mediated pressor responses in pithed rats fed diets with different calcium contents.

Results of many clinical and experimental studies indicate an inverse relationship between dietary calcium and the prevalence of hypertension. Our study was designed to evaluate the alterations in arterial blood pressure and the changes in alpha-adrenoceptor-mediated vascular reactivity in normotensive Sprague-Dawley and spontaneously hypertensive rats (SHR) fed from weaning (3 weeks of life) three diets: normal calcium (Ca 1%), low calcium (Ca 0.1%), and high calcium (Ca 2.5%). The systolic and the diastolic arterial blood pressures were measured weekly by the tail cuff method. The plasma calcium levels in the animals were also measured regularly by colourimetric methods, and the alpha-adrenoceptor-mediated vascular reactivity was evaluated by measuring the pressor responses to alpha-adrenoceptor agonists in pithed rats. These determinations were carried out at the end of the feeding periods (9 weeks of life in Sprague-Dawley rats and 20 weeks of life in SHR) and also at the moments when maximal differences in arterial blood pressure were observed between the conscious animals fed the normal calcium diet and those fed the other two diets. Dietary calcium deficiency increased arterial blood pressure in both strains but calcium supplements were effective to lower this only in hypertensive animals. The plasma calcium levels were altered in both strains when calcium administration was not normal. The low-calcium diet did not modify the pressor responses to either the alpha(1)-adrenoceptor agonist, methoxamine, or the alpha(2)-adrenoceptor agonist, B-HT 920 (5-allyl-2-amino-5,6,7, 8-tetrahydro-4H-thiazolo-(4,5-D)-acepin-dihydrochloride, talixepole), in the normotensive and the hypertensive rats. On the contrary, the high-calcium diet caused a definite decrease in alpha(1)- and alpha(2)-adrenoceptor-mediated vascular reactivity in both strains. The changes in the alpha-adrenoceptor-mediated vasoconstrictor responses were observed in pithed 9-week old Sprague-Dawley rats and in pithed 20-week old SHR, but none were observed in pithed 15-week old SHR, although at this age maximal differences in arterial blood pressure between the animals fed the high- and the normal calcium diet were observed. The results of this study suggest that the mechanisms implicated in the effects of dietary calcium supplements on arterial blood pressure are clearly different from the mechanisms, which bring about changes in arterial blood pressure when the diet is deficient in calcium. The results of this study also show that calcium administration causes variations in alpha-adrenoceptor-mediated vascular reactivity, but this is probably not the only mechanism implicated in the calcium effect on arterial blood pressure.

Adrenergic alpha-Agonists↗

PubMed1999

Sodium-dependent glutamate transport in Müller glial cells: regulation by phorbol esters.

The regulation of the Na(+)-dependent high affinity glutamate/aspartate transporter system expressed in cultured Müller glia cells from chick retina was studied. Treatment of the cells with the Ca(2+)/diacylglycerol dependent protein kinase C (PKC) activator, phorbol 12-tetradecanoil-13-acetate (TPA) produced a decrease in [(3)H]D-aspartate uptake which was reversed by staurosporine and partially by H7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochoride], two PKC inhibitors. Long-term treatment with TPA resulted in a drastic decrease in the uptake activity, correlated with a substantial fall in the expression of the transporter protein. These findings suggest that PKC is involved in transport modulation at two different levels: phosphorylation and transporter expression in retinal Müller glial cells.

ATP-Binding Cassette Transporters↗

PubMed1999

Low affinity Fc gamma receptors on murine macrophages: mitogen-activated protein kinase activation and AP-1 DNA binding activity.

Mouse macrophage cell lines such as J774 express Fc receptors for IgG2a immune complexes, which upon binding of the proper ligand, trigger several signal transduction pathways. A surface to nucleus signaling through these receptors has been demonstrated. We describe here the activation of the mitogen-activated protein kinase (MAPK) and an increase in the binding of the activator protein 1 (AP-1) to DNA upon receptor stimulation. The described effects are only partially blocked by inhibitors of the Ca2+/diacylglycerol-dependent protein kinase (PKC), suggesting that differential signaling pathways are activated upon receptor cross-linking and that they converge at or above the MAPK level. These results pave the way to our understanding of Fc gammaR cross-linking induced gene expression regulation.

Animals↗

PubMed1999

Entamoeba histolytica: signaling through G proteins.

The intracellular signaling pathways of Entamoeba histolytica are largely unknown. Although the expression of guanine nucleotide binding proteins (G proteins) is expected from functional studies, their biochemical characterization remains elusive in this protozoan. Using a combination of biochemical and immunological studies, we provide strong evidence for the presence of a Gs protein in amoeba. Our results strengthen our understanding of the signal transduction mechanisms in E. histolytica as potential sites of a new therapeutic strategy.

Adenylyl Cyclases↗

PubMed1999

Relationship between pharmacokinetic parameters of gentamicin and patient characteristics and/or clinical data in patients with solid organ tumours.

Gentamicin monitoring and the selection of the initial dosage are generally based on the relationship between pharmacokinetic parameters of gentamicin (GPP) and patient characteristics and/or clinical data (PC). However, the number of studies about this relationship in cancer patients is limited. Therefore, the main objective of the present study was to evaluate the relationship between GPP and PC in cancer patients and to identify different subgroups within this group of patients with unique relationship models between GPP and PC. A total of 198 cancer patients were included in the study. Firstly, GPP were estimated by the Sawchuk and Zaske regression method. Then, a linear regression analysis was performed to investigate the relationship between GPP and PC, and lastly subgroups with unique models were identified by comparing their regression models. The results revealed that the variable which was the best predictor of the distribution volume of gentamicine was the dosing weight (DW = IBW + (ABW-IBW), ABW being the actual body weight and IBW the ideal body weight). Creatinine clearance (CLCR) measured by a 24-hour urine collection (CLCRu) was the best predictor of gentamicin clearance (CL). When this value is not available, the CLCR estimated by the formula of Crockcroft and Gault (C-G), can be used. When the C-G formula was used, unique models to predict CL from CLCR were identified for patients who were obese, patients who had received high-dose chemotherapy and, for subjects who had never developed aplasia following chemotherapy. Whichever the model used, the results showed that some variability in pharmacokinetic parameters of gentamicin was not explained by the models, especially in some groups of patients.

Creatinine↗

PubMed1999

Economic evaluation of Viaflex with vial adapter in a unit-dose drug distribution system.

The cost of parenteral admixtures has an important impact on the hospital budget. Recently, a Viaflex with vial adapter (named 'minibag plus' in some countries) has been commercialized in order to facilitate parenteral admixture preparation. In the present study a preparation using Viaflex with a vial adapter has been economically compared with a preparation with a traditional Viaflex (without adapter) in a centralized unit or in nursing wards in a unit-dose drug distribution system. A cost-analysis was conducted from the hospital point of view. Direct costs were considered: these included supplies and human resources. Differences in the whole process between the two types of Viaflex were analysed. The process included: purchasing, reception, storage, medical order record, preparation in the Pharmacy Service (PS), delivery from the PS to the nursing unit, preparation by the nurse, return of unused material to the PS. Human resource costs were estimated by time counting and multiplying by the average salary. To estimate wasted material, drug and supplies delivered from the PS and returned to the PS were counted during 26 days. With the new Viaflex costs are reduced by 30% in comparison with drug dilution using the traditional Viaflex in a centralized unit of the PS, and by 13.4% in comparison with preparation with the traditional Viaflex in the nursing ward. In addition it can be estimated that contamination risk with the new Viaflex is lower than preparation in the nursing ward with the traditional Viaflex. Therefore, owing to its lower cost we recommend the use of Viaflex with vial adapter for drug dilution for those vials that are compatible with the system.

Costs and Cost Analysis↗

PubMed1999

Stat3 participates in the metabotropic glutamate signaling pathway in Bergmann glial cells.

Purkinje cells establish a glutamatergic synapse with the parallel fibers in the cerebellum. Bergmann glial cells surround this synapse. The transcription factor Stat3, highly expressed in cerebellum, is present in cultures of chick Bergmann glia. Treatment of these cells with L-glutamate induces the tyrosine-phosphorylation of Stat3. The maximal phosphorylation was observed after 15 min and by 30 min returned to basal levels. This effect correlated with Stat3 translocation to nucleus and the appearance of a retarded band in gel mobility shift assays. The effects observed with L-glutamate were mediated through metabotropic glutamate receptors. These results further support the notion that glial cells respond to L-glutamate through changes in the existing proteins and also in gene expression regulation.

Animals↗