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Biomedical subjects

R Vargas

Publications and source records attributed to R Vargas.

At least 19 recordsLinked to original sources
PubMed2006

[Review of the interference between the most commonly prescribed drugs and clinical analyses at the Primary Health Care Centre of L'Hospitalet de Llobregat].

OBJECTIVE: To analyse the concordance of published information on probable drug interactions and the results of clinical analyses. DESIGN: Bibliographical review of the 50 most commonly prescribed drug products at the Primary Health Centre of L'Hospitalet de Llobregat, Barcelona, Spain, in 2002 and 2003. DATA SOURCE: Six bibliographical sources consisting of drug product catalogues and reference books. MEASUREMENTS: Interference with the 56 drug products studied. RESULTS: Most theoretical interference belonged to the therapeutic group of anti-inflammatory drugs. The drug products with most interference were hydrochlorothiazide (diuretic) and gliclazide (lipid lowering). The most frequent interference was in the increase of transaminases, thrombocytopaenia, leukopaenia, hyperglycaemia, and hyperuricaemia. Only in 12% of the points of interference analysed was the rate of concordance among the various bibliographical sources reviewed higher than 50%. The highest rate of concordance was found in the diuretics. CONCLUSIONS: Consultation of a single bibliographical source does not necessarily ensure the obtaining of reliable data on possible drug interference. This study demonstrates the need to standardize information on drug interference and to include the medication that the patient follows on the analysis application form.

Drug Interactions↗
PubMed2005

Signal intensity of MR-images of thigh muscles following acute open- and closed chain kinetic knee extensor exercise - index of muscle use.

Exercise-induced shifts in signal intensity (SI) of magnetic resonance (MR) images were examined to assess indirectly muscle use in closed- and open-chain knee extensor exercises. Eight men performed five sets of 8-12 repetitions in the leg press (LP) and the seated knee extension (KE) exercises at 50, 75 and 100%, respectively of the 5 x 10 repetition maximum (RM) load. Prior to exercise and after each load setting, images of the thigh were obtained. The increase in SI (Delta SI) of the quadriceps at 100% load was greater (P < 0.05) after KE (32.1 +/- 9.0%) than after LP (21.9 +/- 9.2%). Regardless of load, the four individual muscles of the quadriceps showed similar changes in SI after LP. The three vastii muscles showed comparable increases in SI after KE. M. rectus femoris showed greater (P < 0.05) Delta SI than the vastii muscles at 100%. Neither exercise produced increase in SI of mm. semimembranosus, semitendinosus, gracilis or biceps femoris. Mm. adductor magnus and longus showed increased (13.3 +/- 6.5%; P < 0.05) SI after LP, but not after KE, at 100% load. The present data also infer greater involvement of the quadriceps muscle in the open-chain knee extension than in the closed-chain leg press exercise. The results of the current investigation also indicate similar over-all use among the three vastii muscles in LP and KE, but differential m. rectus femoris use between the two exercises. This report extends the merits of the MR imaging technique as an aid to study individual muscle involvement in a particular exercise task.

Exercise↗
PubMed2001

Omapatrilat versus lisinopril: efficacy and neurohormonal profile in salt-sensitive hypertensive patients.

Omapatrilat, a vasopeptidase inhibitor, simultaneously inhibits neutral endopeptidase and ACE. The efficacy and hormonal profile of omapatrilat and lisinopril were compared in salt-sensitive hypertensive patients. On enrollment, antihypertensive medications were withdrawn, and patients received a single-blind placebo. On day 15, salt-sensitivity determinations were made. Salt-sensitive hypertensive patients returned within 5 to 10 days for baseline evaluations of ambulatory diastolic blood pressure, ambulatory systolic blood pressure, and atrial natriuretic peptide. Salt-sensitive hypertensive patients were randomized to receive double-blind omapatrilat (n=28) or lisinopril (n=33) at initial doses of 10 mg for 1 week, increasing to 40 and 20 mg, respectively, for an additional 3 weeks. Ambulatory blood pressure and urinary atrial natriuretic peptide were assessed at study termination. Both omapatrilat and lisinopril significantly reduced mean 24-hour ambulatory diastolic and systolic blood pressures; however, omapatrilat produced significantly greater reductions in mean 24-hour ambulatory diastolic blood pressure (P=0.008), ambulatory systolic blood pressure (P=0.004), and ambulatory mean arterial pressure (P=0.005) compared with values from lisinopril. Both drugs potently inhibited ACE over 24 hours. Omapatrilat significantly (P<0.001) increased urinary excretion of atrial natriuretic peptide over 0- to 24-hour (3.8-fold) and 12- to 24-hour (2-fold) intervals; lisinopril produced no change. Omapatrilat significantly (P<0.001) increased urinary excretion of cGMP over the 0- to 24- and 4- to 8-hour intervals compared with that from lisinopril. Neither drug had a diuretic, natriuretic, or kaliuretic effect. In conclusion, in salt-sensitive hypertensive patients, omapatrilat demonstrated the hormonal profile of a vasopeptidase inhibitor and lowered ambulatory diastolic and systolic blood pressures more than lisinopril.

Adult↗
PubMed2001

Structural criteria for the rational design of selective ligands. 3. Quantitative structure-stability relationship for iron(III) complexation by tris-catecholamide siderophores.

We present an extended MM3 model for catecholamide ligands and their Fe(3+) complexes and the application of this model to understand how ligand architecture effects Fe(3+) binding affinity. Force field parameters were fit to geometries and energies from electronic structure calculations, and to crystal structure data. Optimized geometries are reported for phenol, acetamide, the phenol-phenol dimer, the acetamide-phenol dimer, and N-methylsalicylamide (HMSA) at the BLYP/DZVP2/A2 level of theory. Optimized geometries and relative energies are reported for the pseudo-octahedral ground state and the trigonal planar transition state of [Fe(CAT)(3)](3)(-) at the VWN/DZVP2/A1 level of theory. The MM3 model is validated by comparison of calculated structures with crystal structures containing 1,2-dihydroxybenzene (H(2)CAT) and 2,3-dihydroxy-N-methylbenzamide (H(2)MBA) fragments, crystal structures of [Fe(CAT)(3)](3)(-) and tris-catecholamide Fe(3+) complexes, and comparison of MM3 (6.8 kcal/mol) and VWN (5.9 kcal/mol) barriers for intramolecular octahedral inversion in [Fe(CAT)(3)](3)(-). The MM3 model also rationalizes the higher inversion barrier (14 to 18 kcal/mol) reported for [Ga(N,N-diisopropylterephthalamide)(3)](3)(-) ([Ga(DIPTA)(3)](3)(-)). Conformational searches were performed on enterobactin (H(6)ENT), 1,3,5-tris(2,3-dihydroxybenzamidomethyl)-2,4,6-triethylbenzene (H(6)EMECAM), 1,3,5-tris(2,3-dihydroxybenzamidomethyl)-2,4,6-trimethylbenzene (H(6)MMECAM), 1,3,5-tris(2,3-dihydroxybenzamidomethyl)benzene (H(6)MECAM), and 1,5,9-N,N',N' '-tris(2,3-dihydroxybenzoyl)cyclotriazatridecane (H(6)-3,3,4-CYCAM) and Fe(3+) complexes with each of these ligands. A conformational search also was done on the Fe(3+) complex with the 2,2',2' '-tris(2,3-dihydroxybenzamido)triethylammonium cation (H(7)TRENCAM(+)). The relationship between calculated steric energies and measured thermodynamic quantities is discussed, and linear correlations between formation constants and steric energy differences are reported. Extrapolation to zero strain predicts formation constants 8 +/- 5 orders of magnitude higher than that exhibited by ENT (10(49)) are possible. This prediction is supported by a formation constant of 10(63) estimated from the formation constant of [Fe(2,3-dihydroxy-N,N-dimethylbenzamide)(3)](3)(-) ([Fe(DMBA)(3)](3)(-)) by considering the entropic consequences of connecting three DMBA ligands to a rigid backbone. Structural criteria for the identification of improved tris-catecholate ligand architectures are presented.

Algorithms↗
PubMed2001

Effect of Cirsium pascuarense on blood glucose levels of normoglycaemic and alloxan-diabetic mice.

Blood glucose levels of normal and alloxan-treated diabetic mice were determined after i.p. administration of various doses of the hexane, chloroform and methanol extracts of Cirsium pascuarense. From the data obtained, it is concluded that the i.p. administration of 100, 150 and 200 mg/kg of hexane extract of this plant produced a significant hypoglycaemic effect in normal as well as in diabetic mice. In addition, the extracts altered glucose tolerance in alloxan induced diabetic rats. Chloroform and methanol extracts did not produce any significant change in blood glucose levels.

Alloxan↗
PubMed2001

A reversible abnormal form of myelin: an X-ray scattering study of human sural and rat sciatic nerves.

A sural nerve dissected from a recently dead patient displayed an unusual X-ray diffraction pattern, suggesting that in situ and at the time of the patient's death the myelin sheaths were in a swollen state. Diffraction patterns of the swollen type were also recorded from: (1) a sural nerve from the corpse of a neurologically healthy person after soaking the nerve with Ringer solution at pH 5.5; (2) sciatic nerves dissected from rat cadavers at increasing time after death. In all the cases the swollen patterns reversed to the native type upon superfusion with Ringer solution at pH 7.3. The postmortem effect is to decrease the pH of the fluids surrounding the nerves in the cadavers. Our experiments show that the early postmortem processes have the effect of acidifying PNS nerves and that as a consequence of acidification the myelin sheaths swell.

Animals↗
PubMed2001

Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension.

BACKGROUND: African Americans with hypertension, particularly those with more severe blood pressure elevations, are generally less responsive to monotherapy from any antihypertensive class. These patients usually require treatment with drugs from > or = 2 antihypertensive classes to achieve adequate blood pressure control. OBJECTIVE: The purpose of this study was to assess the antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide (HCTZ) in African American adults with mild to moderate hypertension. METHODS: In this 12-week, multicenter, double-blind, randomized, parallel-group, placebo-controlled study, African American patients were randomized in a 3:3:1 ratio to I of 3 treatment groups: placebo, losartan monotherapy (50 to 150 mg), or losartan plus HCTZ (50/0 to 50/12.5 to 100/25 mg). Doses were titrated at weeks 4 and 8 if sitting diastolic blood pressure (SiDBP) was > or = 90 mm Hg. Safety was assessed by determining the incidence of clinical and laboratory Adverse events and evaluating mean changes in pulse, body weight, electrocardiographic parameters, and laboratory test results. RESULTS: A total of 440 patients were randomized-188 to placebo, 193 to losartan monotherapy, and 59 to losartan/HCTZ; 391 completed the study. At week 12, the response rate with losartan monotherapy was 45.8%, with a significant (P < or = 0.01) lowering in mean SiDBP by 6.6 mm Hg compared with placebo; the response rate with placebo was 27.2%, with a mean SiDBP reduction of 3.9 mm Hg. Sitting systolic blood pressure (SiSBP) was significantly lowered with losartan monotherapy, by 6.4 mm Hg, compared with placebo (reduction of 2.3 mm Hg). The response rate with losartan/ HCTZ was 62.7%, with reductions in SiSBP and SiDBP of 16.8 mm Hg and 10.8 mm Hg, respectively (P < or = 0.01 vs placebo and losartan monotherapy). The incidence of clinical adverse events was comparable in the 3 treatment groups. CONCLUSIONS: The results of this study suggest that in African American patients, losartan monotherapy was significantly more effective than placebo in lowering SiSBP and SiDBP. Moreover, the losartan/ HCTZ combination regimen resulted in significant and clinically meaningful additional reductions in SiSBP and SiDBP compared with losartan monotherapy or placebo. Losartan monotherapy and the losartan/HCTZ regimens were generally as well tolerated as placebo.

Black or African American↗
PubMed2001

Effect of food on the pharmacokinetics of a single oral dose of moxifloxacin 400mg in healthy male volunteers.

OBJECTIVE: To investigate the effects of concomitant food intake on the pharmacokinetics of a single oral dose of moxifloxacin 400mg. DESIGN: This was a randomised 2-way nonblinded crossover study in healthy volunteers. PARTICIPANTS: 18 young, healthy, male volunteers were enrolled in the study, of whom 16 were considered evaluable for the pharmacokinetic analysis. METHODS: Moxifloxacin was given under 2 conditions separated by a 1-week washout period: fasted and fed (immediately after a standardised high fat breakfast). Concentrations of moxifloxacin in serum were determined by a validated high performance liquid chromatography procedure with fluorescence detection. OUTCOME MEASURES: Pharmacokinetic parameters such as maximum concentration (Cmax), time to reach Cmax (tmax), area under the concentration-time curve from zero to 48 hours (AUC48h), AUC from zero extrapolated to infinity (AUCinfinity) and elimination half-life (t1/2z) were estimated using noncompartmental methods. The natural logarithms of AUC and Cmax were analysed using analysis of variance. Bioequivalence of the 2 treatments was determined at the 5% significance level with the two 1-sided tests procedure and limits of 80% and 125% for AUC and 70 to 143% for Cmax. RESULTS: The mean serum concentration versus time profiles were similar between the 2 treatments. The geometric mean AUCinfinity values under fed and fasted conditions were almost identical, 37.7 versus 38.5 mg/L x h, respectively [90% confidence interval (CI) of the ratio of fed versus fasted based on geometric least-square means was 0.95, 1.00]. Geometric mean Cmax values were slightly reduced by food, 2.5 versus 2.8 mg/L, respectively (90% CI of fed versus fasted based on geometric least-square means was 0.78, 0.98). The absorption of moxifloxacin seems to be mildly delayed because of the effect of food; the median tmax values were 1.0 and 2.5 hours for fasted and fed conditions, respectively. The single oral dose of moxifloxacin 400mg was well tolerated when taken with and without food.

Administration, Oral↗
PubMed2000

Influence of renal function on the pharmacokinetics of cerivastatin in normocholesterolemic adults.

OBJECTIVE: The influence of impaired renal function on the pharmacokinetics of single and multiple doses of cerivastatin was evaluated in this nonrandomized, non-blinded, 7-day, multiple-dose study. METHODS: Thirty-five adults between the ages of 21 years and 75 years with normal renal function (CL(CR) >90 ml/min/1.73 m2, n = 9), or patients with either mild (CL(CR) 61 ml/min/1.73 m2 to < or =90 ml/min/1.73 m2, n = 9), moderate (CL(CR) 30 ml/min/1.73 m2 to < or =60 ml/ min/1.73 m2, n = 8), or severe (CL(CR) <30 ml/min/ 1.73 m2, but not on dialysis, n = 9) renal impairment were given cerivastatin 0.3 mg daily each evening for 7 days. The steady-state pharmacokinetics of cerivastatin, including the area under the concentration-time curve (AUC)0-24, peak plasma concentration (Cmax), time to reach Cmax (tmax) and elimination half-life (t1/2), were determined on day 1 and day 7. The logarithm of the pharmacokinetic variables was analyzed using analysis of variance (ANOVA). Safety assessments included physical examination, fundoscopy, vital signs, electrocardiogram (ECG), adverse events, and laboratory safety indices. RESULTS: The day-1 AUC in patients with mild renal impairment was similar to that of patients with normal function (19.6 microg/h/l vs 19.2 microg/h/l, respectively). However, the AUC for cerivastatin patients with moderate or severe renal impairment was 40-60% higher (30.8 microg/h/l and 29.0 microg/h/l, respectively). Cmax values for patients with normal, mild, moderate, and severe renal impairment were 3.3, 3.4, 4.6, and 5.2 microg/l, respectively. This modest increase in plasma cerivastatin levels is nearly equivalent to a 0.4-mg daily dose, which has been recently approved in the United States. The mean t1/2 of cerivastatin was less than 4.5 h in all patients, indicating that renal dysfunction did not promote cerivastatin accumulation. This observation was confirmed by the finding that the cerivastatin plasma levels on day 1 and day 7 were similar in all patient groups. Furthermore, the mean AUC and Cmax values for both demethylated and hydroxylated cerivastatin were similar in the patients with the most severe renal dysfunction to the corresponding values in healthy subjects. Cerivastatin was well tolerated in all patients irrespective of renal function. Adverse events were observed in 37% of the subjects; nearly all were mild and generally of short duration, and most resolved without intervention. Incidence of adverse events was similar across all three renal groups and the control group. There were no clinically significant laboratory changes other than those consistent with renal disease. CONCLUSION: This study demonstrates that dosage adjustment of the daily 0.3-mg cerivastatin dose in patients with significant renal impairment is likely unnecessary.

Adult↗
PubMed2000

Malnutrition and myelin structure: an X-ray scattering study of rat sciatic and optic nerves.

Taking advantage of the fast and accurate X-ray scattering techniques recently developed in our laboratory, we tackled the study of the structural alterations induced in myelin by malnutrition. Our work was performed on sciatic and optic nerves dissected from rats fed with either a normal or a low-protein caloric diet, as a function of age (from birth to 60 days). By way of electrophysiological controls we also measured (on the sciatic nerves) the height and velocity of the compound action potential. Malnutrition was found to decrease the amount of myelin and to impair the packing order of the membranes in the sheaths.

Aging↗
PubMed2000

Antenatal Bartter syndrome with sensorineural deafness: refinement of the locus on chromosome 1p31.

BACKGROUND: Recently a locus for antenatal Bartter syndrome associated with sensorineural deafness was mapped to human chromosome 1p31 in a single consanguineous Bedouin family (Brennan et al. Am J Hum Genet 1998; 62: 355-361). METHODS: By haplotype analysis we demonstrate linkage to this locus in nine consanguineous families with antenatal Bartter syndrome associated with sensorineural deafness. RESULTS: The critical interval compatible with linkage was refined to 4.0 cM by two novel recombinational events with markers D1S2661 and D1S475. CONCLUSION: We thereby confirmed this gene locus and distinguished this clinical subtype from other variants of Bartter syndrome as a new disease entity.

Bartter Syndrome↗
PubMed2000

Cirrhosis does not affect the pharmacokinetics and pharmacodynamics of clopidogrel.

Clopidogrel, a new platelet ADP receptor antagonist used for the prevention of vascular ischemic events, is converted to an active metabolite via the cytochrome P450 system. Patients with cirrhosis may not metabolize drugs normally and may, in addition, have a number of defects in the coagulation system. To assess the effect of cirrhosis on the pharmacokinetics and pharmacodynamics of clopidogrel, the authors performed an open-label, parallel-group study of 12 patients with Child-Pugh Class A or B cirrhosis and 12 matched controls. All 24 subjects received clopidogrel 75 mg PO QD for 10 days. Pharmacokinetics of clopidogrel and the major metabolite SR 26334 were analyzed on Days 1 and 10; pharmacodynamics were assessed by the inhibition of ADP-induced platelet aggregation and by bleeding time prolongation factor. Pharmacokinetic analysis of clopidogrel was limited due to low plasma concentrations arising from rapid hydrolysis to SR 26334. The Cmax at SS for clopidogrel was higher in cirrhotics than in normals. However, exposures to the metabolite SR 26334, as measured by AUC(tau), were comparable. At Day 10, there was not a statistically significant difference in mean inhibition of platelet aggregation (49.2% +/- 38.6% in cirrhotics vs. 66.7% +/- 7.5% in normals) or in bleeding time prolongation factor (1.64 +/- 0.49 in cirrhotics vs. 1.54 +/- 0.87 in normals) between groups. No significant adverse events, including bleeding events, were reported. In conclusion, there were no significant differences in the pharmacokinetics and pharmacodynamics of clopidogrel in this group of subjects with cirrhosis and matched normals. Therefore, no dosage adjustment of clopidogrel is required in patients with Child-Pugh Class A or B cirrhosis.

Adult↗
PubMed1999

Antiurolithiatic activity of Raphanus sativus aqueous extract on rats.

The aqueous extract of the bark of Raphanus sativus was tested for its antiurolithiatic and diuretic activity. The urolithiasis was experimentally induced by implantation of zinc disc in the urinary bladder of rats. Significant decrease in the weight of stones was observed after treatment in animals which received aqueous extract in comparison with control groups. This extract showed an increase in the 24 h urine volume as compared to the control.

Animals↗
PubMed1999

Long-term results of the Spanish trial on treatment and survival of patients with predominantly mild heart failure.

A randomized open-label clinical trial was conducted to determine whether mortality, readmission, or quality of life differed between heart failure patients managed with captopril plus diuretics and those with digoxin plus diuretics. A total of 345 heart failure patients in New York Heart Association functional classes 2 and 3 without atrial fibrillation, dyspnea of bronchopulmonary origin, or hypertension not controlled with diuretics was randomized for digoxin (n = 175) or captopril (n = 170) treatment and followed up for a median of 4.5 years. Socioeconomic, demographic, electrocardiographic, echocardiographic, spirometric, and chest radiograph data were obtained at the initial examination. In a random sample of half the patients, ergometric, echocardiographic, and Holter records were obtained at entry and at 3 and 18 months. Patients were followed up for > or = 3 years. The end points were mortality, hospitalization for cardiac events, deterioration in quality of life, worsening of functional class, and need for digoxin or captopril in the captopril and digoxin groups, respectively. The trial had to be terminated prematurely owing to the difficulty in finding candidates free of angiotensin-converting enzyme (ACE)-inhibitor treatment. Baseline patient characteristics were similar in both groups. From the clinical point of view, only the 48-month mortality was relevantly lower (20.9 vs. 31.9%, respectively) among patients treated with captopril than that in those receiving digoxin (log rank test, p = 0.07). No statistically or clinically relevant differences were found in other end points or adverse effects. The results suggest but do not confirm the hypothesis that captopril treatment in mild to moderate heart failure might provide better long-term survival than digoxin.

Aged↗
PubMed1999

A survey of prescribing patterns for tuberculosis treatment amongst doctors in a Bolivian city.

SETTING: A sample survey of knowledge about prescribing tuberculosis treatment among private physicians in the city of Santa Cruz, Bolivia. OBJECTIVES: To study the anti-tuberculosis regimens prescribed by private physicians and to assess the number of tuberculosis patients treated by them. DESIGN: Questionnaire survey of a random sample of 401 private physicians in Santa Cruz. RESULTS: Of the 401 physicians, 165 (41%) could not be located or did not want to participate. Among the 236 completed questionnaires, 137 physicians (58%) stated that they did not see patients with tuberculosis, 16 (7%) referred them to other centres and 83 (35%) treated them in their practice. Among 80 prescribed regimens that could be evaluated there were 58 different regimens: 17 (21%) followed the National Tuberculosis Control Programme's standard regimen, but overall 35 regimens (60%) were incorrect-18 regimens (31%) were non-curative and 17 (29%) could not be recommended. Frequent errors were the prescription of medications not available in the market (7%) or not included in the national regimen (34%), the prescription of insufficient medications (9%), or of only one in the continuation phase (16%), or for too short (9%), or too long (12%) a period. Eighty physicians estimated that they attended in their practice an average total of 404 patients with tuberculosis per month. CONCLUSIONS: A significant number of physicians in private practice did not adhere to the standard norms for prescribing anti-tuberculosis treatment. This study also suggests that in the city of Santa Cruz, Bolivia, there is a not insignificant number of patients with tuberculosis treated outside the National Tuberculosis Control Programme.

Antitubercular Agents↗
PubMed1999

Effects of high resistance training in patients with myotonic dystrophy.

Nine ambulatory subjects with myotonic dystrophy participated in a supervised 12-week progressive high-resistance training program. Knee extensor muscles were trained 3 times a week with free weights, 3 x 10 repetitions at 80% of 1RM. One leg was randomly chosen for training and the other served as control. Six patients completed the training program. In the trained leg, 1RM increased from 16.4 +/- 3.4 kg to 21.8 +/- 2.6 kg (p = 0.0002). There was no difference between pre- and post-training concentric or eccentric isokinetic values at 30 degrees/second in either leg. Muscle biopsy from m. vastus lateralis in the trained leg revealed no systematic difference in the degree of histopathological abnormalities before and after training. After training, there was a tendency toward increase in cross-sectional area of type I muscle fibres. However, the number of subjects was too small to draw conclusions regarding the effects of training on the histopathological changes. Magnetic resonance imaging revealed no difference in the m. quadriceps area after training. In conclusion, patients with myotonic dystrophy improved their muscle strength without any observed negative side effects after a 12-week high-resistance training program.

Adult↗