Transvenous cardioversion and defibrillation of ventricular tachyarrhythmias: current status and future directions.
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Biomedical subjects
Publications and source records attributed to R Calvo.
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Phenylbutazone and clofibric acid, two drugs strongly bound to human albumin, produce low readings of albumin content in serum when the bromocresol green immediate reaction is used. This abnormality is observed at drug concentrations within the range obtained during therapeutic use, and tends to be more marked in diluted samples of serum. Abnormally low values of albumin content are also obtained when the bromocresol green method is used in uremic sera, and the disparity seems related to the degree of carbamylation of these samples. The reported interferences are great enough in some cases as to suggest that the use of the immediate reaction between bromocresol green and serum should not be considered a valid measure of albumin content when these factors cannot be totally excluded.
Electron paramagnetic resonance (EPR) spectra of the reduced quinone-iron acceptor complex in reaction centers were measured in a variety of environments and compared with spectra calculated from a theoretical model. Spectra were obtained at microwave frequencies of 1, 9, and 35 GHz and at temperatures from 1.4 to 30 K. The spectra are characterized by a broad absorption peak centered at g = 1.8 with wings extending from g approximately equal to 5 to g less than 0.8. The peak is split with the low-field component increasing in amplitude with temperature. The theoretical model is based on a spin Hamiltonian, in which the reduced quinone, Q-, interacts magnetically with Fe2+. In this model the ground manifold of the interacting Q-Fe2+ system has two lowest doublets that are separated by approximately 3 K. Both perturbation analyses and exact numerical calculations were used to show how the observed spectrum arises from these two doublets. The following spin Hamiltonian parameters optimized the agreement between simulated and observed spectra: the electronic g tensor gFe, x = 2.16, gFe, y = 2.27, gFez = 2.04, the crystal field parameters D = 7.60 K and E/D = 0.25, and the antiferromagnetic magnetic interaction tensor, Jx = -0.13 K, Jy = -0.58 K, Jz = -0.58 K. The model accounts well for the g value (1.8) of the broad peak, the observed splitting of the peak, the high and low g value wings, and the observed temperature dependence of the shape of the spectra. The structural implications of the value of the magnetic interaction, J, and the influence of the environment on the spin Hamiltonian parameters are discussed. The similarity of spectra and relaxation times observed from the primary and secondary acceptor complexes Q-AFe2+ and Fe2+Q-B leads to the conclusion that the Fe2+ is approximately equidistant from QA and QB.
Procaine esterase activity in plasma from patients with renal failure is decreased by 40%. Since cyanate is formed from urea and readily carbamylates certain blood proteins, a possible role for cyanate in the depression of plasma esterase activity in uraemic patients was considered. However, in vitro carbamylation of normal plasma in a range similar to that detected in uraemic patients did not influence procaine esterase activity. Kinetic analysis of the reaction showed that the maximal hydrolyzing capacity but not the Km in uraemic plasma was diminished (5.0 +/- 0.3 X 10(-5) moles hydrolyzed per litre of plasma per minute and a Km of 3.9 +/- 0.2 X 10(-5) mol/l in plasma from normal volunteers as compared to 3.1 +/- 0.1 X 10(-5) mol/l/min and 3.5 +/- 0.2 X 10(-5) ml/l in plasma from patients with renal failure). Therefore, not carbamylation but rather a decrease in enzyme synthesis is the likely explanation for the lower rate of procaine hydrolysis in uraemic plasma.
The effects of in vitro carbamylation of plasma with potassium cyanate on the binding of sulfisoxazole and diazepam have been investigated. Incubation of plasma with potassium cyanate produced varying degrees of carbamylation of plasma proteins which were associated with a decrease in the binding of sulfisoxazole (100 mg/l), a drug bound to site I on the human albumin. Scatchard plots showed that this decreased binding resulted from a decrease in affinity without changes in the number of binding sites. Similar changes were detected in uremia. Carbamylation of plasma proteins did not affect the binding of diazepam (3 mg/l), a drug bound to site II. The plasma protein binding of sulfisoxazole and diazepam was decreased in samples from uremic patients. Charcoal treatment did not modify the binding of sulfisoxazole to normal or carbamylated plasma while it reduced, but did not normalize, the binding defect in uremic plasma. On the other hand, charcoal treatment brought the binding of diazepam in uremic plasma to normal values. It seems that only drug binding site I is carbamylated in uremia, while competitive displacers bind to sites I and II.
Plasma protein binding of etomidate, an intravenous anesthetic agent of basic nature, has been studied in healthy subjects of different age groups and in patients with chronic respiratory insufficiency. No differences were detected in the plasma protein binding of etomidate between young children and young adults, but elderly subjects exhibited decreased binding. Low levels of serum albumin may account in part for this decreased binding, but differences in the amount of etomidate bound per mol of albumin and in affinity constants for the binding were also apparent between young adults and elderly individuals. Although plasma protein binding of etomidate may also be decreased in patients with chronic respiratory insufficiency, further studies are needed to clarify this point.
Procaine hydrolysis in vitro has been studied in whole blood, plasma, and washed erythrocytes. Esterase activity was higher in whole blood than in either diluted plasma or resuspended erythrocytes. Eserine and echothiophate specifically inhibited plasma procaine esterase activity, while acetazolamide blocked hydrolysis of procaine by washed erythrocytes. Kinetic studies in whole blood also identified 2 different enzymes. Procaine esterase activity associated with red blood cells was not impaired in patients with renal failure or hepatic cirrhosis, but procaine half-life (t 1/2) in whole blood of normal subjects was longer after 250 mg acetazolamide.
The effects of in vitro carbamylation of plasma with potassium cyanate on drug-protein binding have been investigated. Potassium cyanate added to samples of normal plasma and incubated for 30 to 150 min induced time-related plasma protein carbamylation. Carbamylation of plasma did not influence quinidine protein binding, but resulted in decreased salicylate binding. The increased free fraction of salicylate in plasma correlated with the degree of carbamylation of plasma proteins (r = 0.99; p less than 0.001). Plasma from patients with chronic renal disease showed varying degrees of plasma protein carbamylation, correlating with the values of free plasma salicylate (r = 0.80; p less than 0.05). Scatchard plots for sulfadiazine binding in plasma from patients with uremia and in normal plasma carbamylated in vitro with potassium cyanate showed changes in the 2 groups when compared with those in normal individuals. If cyanate is produced in vivo from urea in patients with uremia, plasma protein carbamylation may play a role in the decreased plasma protein binding of some acidic drugs.
No hydrolysis of etomidate in plasma in vitro was detected in samples from man, horse, cow, sheep, guinea pig or white rabbit. Brown rabbits showed a moderate degree of hydrolysis and it was marked in plasma from Wistar rats. In this species, a single enzyme, an alliesterase, participated in the hydrolysis in plasma. Etomidate did not interfere with the hydrolysis of procaine by plasma pseudocholinesterase in man.
In this multi-clinic double-blind study, patients suffering from insomnia were treated with triazolam 0.5 mg (Halcion) or placebo for 14 days. Four investigators treated 239 patients, 122 on triazolam and 117 on placebo. Thirty-nine patients, 10 on triazolam and 29 on placebo, dropped out for ineffectiveness of the medication and 32 patients, 16 in each group, dropped out for side effects. Analysis of pooled efficacy data showed that triazolam was significantly better than placebo on all efficacy parameters measured, including how much the medication helped the patients sleep, onset of sleep, duration of sleep, duration compared to usual, number of nocturnal awakenings, and feeling of restfulness in the morning. Triazolam did not produce evidence of tolerance development after 2 weeks of treatment. The same variety of side effects occurred on each treatment and primarily included drowsiness, grogginess, headaches, impaired coordination nausea, and dizziness.
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This study was designed to determine whether the surgical procedures for gastroduodenal ulcers influence sulfamethazine (SMZ) absorption and disposition. Prior to and on the average 79 days after surgery, eight patients received 10 mg kg-1 of sulfamethazine orally. Blood samples were obtained at regular intervals over 24 h and urine was collected for 48 h. Vagotomy with pyloroplasty or with gastrojejunostomy had no effect on SMZ kinetics. Vagotomy with partial gastrectomy decreased the SMZ plasma peak concentrations from 43.9 +/- 7.1 (mean +/- SEM) to 17.2 +/- 5.2 micrograms ml-1 (p less than 0.05) and increased the time required to reach this peak from 2.6 +/- 0.8 to 9.8 +/- 2.8 h (p less than 0.05). SMZ rate constant of absorption decreased only slightly (1.22 +/- 0.45 to 0.24 +/- 0.07 h-1) and SMZ bioavailability was not affected at all. In two (out of four) patients, SMZ volume of distribution and total body clearance increased, as reflected in the 41 per cent decrease in the mean area under the SMZ plasma concentration-time curve. No changes were detected in SMZ protein binding. Computer simulations indicated that in some subjects SMZ plasma concentrations at steady state could be 76 per cent lower following vagotomy with partial gastrectomy than before surgery. It was concluded that vagotomy and antrectomy with a gastroduodenostomy or Billroth I reconstruction decreased the rate of SMZ absorption and only in some subjects increased the SMZ volume of distribution and rate of elimination. The possible mechanisms involved in these reported kinetic changes are discussed.
The 24 h urinary excretion of paracetamol and its metabolites following a single oral dose of 1.5 g was compared in two ethnically different Spanish populations: 39 volunteers from the Basque country and 32 from Alicante. The urinary concentrations of unchanged paracetamol and its glucuronide, sulphate, cysteine, and mercapturic acid conjugates were determined by high-performance liquid chromatography. Statistically significant differences in the urinary excretion of unchanged paracetamol and the fractional urinary recovery of each conjugate between subjects from Alicante and subjects from the Basque country were not found. In both populations, an inverse relationship between glucuronide and sulphate conjugation following a bimodal frequency distribution pattern was found. In contrast to paracetamol oxidation, intersubject variation in paracetamol conjugation was negligible. The urinary excretion of unchanged paracetamol was higher in smokers than in nonsmokers. As compared with other studies, the urinary excretion of oxidation-derived paracetamol metabolites in both Spanish populations was intermediate and significantly different than that found in Caucasians from Scotland and West Africans (Ghana). This may determine a susceptibility to paracetamol hepatotoxicity following overdosage in the Spanish population.
Penbutolol is a not cardioselective beta-adrenergic blocking drug; it is lipid soluble and differs in its protein binding from the other members of its group because shows linkage to alpha 1-glycoprotein, with no detectable binding to albumin. AAG levels change during pregnancy and so the binding of [3H]-penbutolol was compared in 11 pregnant patients and in 10 healthy women. Binding was obtained by ultrafiltration and measurement of the free fraction by scintillation spectrometry. The free penbutolol fraction was significantly higher in the pregnant women than in the controls (6.06 +/- 0.34 compared with 3.55 +/- 0.29, P less than 0.001). The AAG levels in the pregnant women were significantly lower (0.40 +/- 0.03 g/l) than in the controls (0.77 +/- 0.06 g/l) (P less than 0.001) which showed a significant correlation with the bound/free penbutolol ratio (r = 0.61, P less than 0.005). On the other hand there was no significant correlation with the extent of penbutolol's protein binding even though the albumin levels were lower in the pregnant women (2.83 +/- 0.17 compared with 4.86 +/- 0.17; P less than 0.001). Penbutolol's nK1a for AAG was lower in pregnant women, and this suggests that the fall in AAG levels is not the only factor involved in the reduced binding of penbutolol in pregnancy.
Protein binding of mianserin and imipramine in vitro was determined in sera from 10 patients with cancer and from 28 drug-free normal subjects. alpha 1-acid glycoprotein (AAG) concentrations ranged from 0.91 +/- 0.04 g/l in control subjects to 2.17 +/- 0.18 g/l in cancer patients. Albumin concentrations ranged from 55.80 +/- 1.68 g/l in control subjects to 39.71 +/- 4.40 g/l, respectively. Serum samples containing concentrations of 100 ng/ml for mianserin and 500 ng/ml for imipramine were ultrafiltered and the free concentration were measured with scintillation spectrophotometer. The mean free percentage of mianserin was significantly less in patients with cancer (8.70 +/- 0.29% in patients vs 14.30 +/- 0.50% in control subjects P < 0.001). A multiple regression analysis revealed a significant contribution of plasma AAG (r2 = 0.56, P < 0.01), but not of albumin to the overall variability in mianserin binding. No correlation was observed between protein binding of imipramine and AAG concentrations in serum of cancer patients. No significant changes were observed for protein binding of imipramine in cancer patients as compared with control subjects. Our results suggest that for antidepressant (AD) drugs, of which the binding depends on AAG, variability in protein binding could be expected in cancer patients. Thus, in cancer therapy, changes in analgesic doses could be necessary with this kind of antidepressant drug.
BACKGROUND: Several studies have shown a growth in the number of visits to accident and emergency (A&E) hospital departments with a high proportion of inappropriate utilization. Methods to identify improper use based on implicit criteria limit the comparisons between hospitals. The aim of this study is to know the proportion of inappropriate attendance's in an A&E department and their associated factors, using a method with objective criteria. METHODS: An instrument based on diagnosis-independent explicit criteria was used to identify inappropriate visits in a random sample of 1845 14-year-old greater patients attended to A&E medical services, and the factors associated with improper demand were analysed. RESULTS: The proportion of inappropriate attendance's was of the 26,8% (495/1. 845). The unadjusted analysis show that the smaller age, absence of comorbidity, spontaneous visit and some diagnostic groups (diseases of the skin, muscle-skeletal, mental, and bad defined symptoms) were associated to a greater proportion of improper use. Upon adjusting the variables through logistics regression, the age, associated pathology, the spontaneous attendance's and diagnostic groups, maintained the association with improper use, but other variables as woman gender, and night hours were also associated to inappropriate utilization. CONCLUSIONS: At least the fourth part of the attendance's in the A&E medical services do not require urgent attention. Inappropriate utilization is associated to characteristic of the patient and the attended process.
Many soils of the Mediterranean region with a semiarid climate are subjected to progressive degradation as a result of water erosion. Biosolids and municipal solid wastes (MSW) were surface-applied once at three rates (40, 80, and 120 Mg ha(-1)) to different plots in a degraded semiarid ecosystem. The study was conducted to determine the effects of such applications on soil chemical properties and native vegetation over a three-year period. Soil N, P, and K initially increased with increasing biowaste application rates, but then decreased over time. Levels of Zn and Cu were higher in MSW than biosolid-treated plots, and increased in both years after application. Concentrations of soil Cd, Pb, Ni, and Cr did not change as a result of biowaste amendment in the study period. The growth of native plants was enhanced by the addition of biowastes. Total plant canopy and plant biomass increased significantly and remained higher in all treatments than in the control plot over the three-year period. The species richness of native plants decreased with increasing biowaste rates. Differences in the development of native plant communities between treatments were observed, and were more remarkable three years after biowaste application. Tissue N, P, K, Zn, and Cu levels increased with the biowaste application rate, but concentrations of tissue Pb, Cd, Ni, and Cr did not increase significantly. Biowastes applied at the rate of 80 Mg ha(-1) gave rise to the most favorable soil and native vegetation results while avoiding environmental risks.