Does Ad Hoc Coronary Intervention Reduce Radiation Exposure? – Analysis of 568 Patients

Background

Advantages and disadvantages of ad hoc percutaneous coronary intervention have been described. However little is known about the radiation exposure of that procedure as compared with the staged intervention.

Objective

To compare the radiation dose of the ad hoc percutaneous coronary intervention with that of the staged procedure

Methods

The dose-area product and total Kerma were measured, and the doses of the diagnostic and therapeutic procedures were added. In addition, total fluoroscopic time and number of acquisitions were evaluated.

Results

A total of 568 consecutive patients were treated with ad hoc percutaneous coronary intervention (n = 320) or staged percutaneous coronary intervention (n = 248). On admission, the ad hoc group had less hypertension (74.1% vs 81.9%; p = 0.035), dyslipidemia (57.8% vs. 67.7%; p = 0.02) and three-vessel disease (38.8% vs. 50.4%; p = 0.015). The ad hoc group was exposed to significantly lower radiation doses, even after baseline characteristic adjustment between both groups. The ad hoc group was exposed to a total dose-area product of 119.7 ± 70.7 Gycm², while the staged group, to 139.2 ± 75.3 Gycm² (p < 0.001).

Conclusion

Ad hoc percutaneous coronary intervention reduced radiation exposure as compared with diagnostic and therapeutic procedures performed at two separate times.     

Population Pharmacokinetics of Micafungin and Its Metabolites M1 and M5 in Children and Adolescents

The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtained from four phase I and two phase III clinical trials. Population pharmacokinetic models were used to simulate the proportion of children who had a steady-state area under the concentration-time curve at 24 hours (AUC₂₄) of micafungin within the 10th to 90th percentile range observed in a population of adults receiving a dose of micafungin with established efficacy for invasive candidiasis (100 mg/day), i.e., 75 to 139 μg · h/ml. Simulated pediatric dosages of 0.5 to 5 mg/kg of body weight/day were explored. A two-compartment model was used that incorporated body weight as a predefined covariate for allometric scaling of the pharmacokinetic parameters. During construction of the model, aspartate aminotransferase and total bilirubin were also identified as covariates that had a significant effect on micafungin clearance. A dose of 2 mg/kg resulted in the highest proportion of children within the predefined micafungin AUC₂₄ target range for invasive candidiasis. Cutoffs of 40 or 50 kg for weight-based dosing resulted in heavier children being appropriately dosed. Thus, dose regimens of 1, 2, and 3 mg/kg/day micafungin are appropriate for the prevention of invasive candidiasis, the treatment of invasive candidiasis, and the treatment of esophageal candidiasis, respectively, in children aged 4 months to <17 years.     

Double balloon pulmonary valvuloplasty: multi-track system versus conventional technique.

OBJECTIVES: To evaluate whether double balloon pulmonary valvuloplasty (DBPV) with the Multi-Track system (MTS) may help to simplify the procedure. BACKGROUND: DBPV is usually required for patients with pulmonary valve stenosis with large annulus. However, it needs two venous accesses and can be technically demanding. METHODS: From 07/03, 20 consecutive patients (19 +/- 10 yrs) with typical pulmonary valve stenosis underwent DBPV using the MTS (G1). The results were compared with those achieved by conventional DBPV performed in a matched historical group of 28 patients (21 +/- 11 yrs; P = NS) (G2). RESULTS: MTS balloons were easily advanced through the skin and inflated across the valve. Similar results were observed in regards to residual gradients (12 +/- 11 vs 14 +/- 10 mm Hg; P = NS) and right ventricular to systemic pressures (0.35 +/- 0.22 vs 0.37 +/- 0.26; P = NS). Procedure and fluoroscopic times were significant lower in G1 (78 +/- 24 vs 126 +/- 28; 15 +/- 12 vs 25 +/- 8 min, respectively; both P < 0.001). There was no major complication. Median follow-up was 1.8 yr for G1 and 5 yr for G2 (P = 0.037). At the last visit, peak instantaneous gradient across the right ventricular outflow tract by echocardiography was a mean 22 +/- 10 mm Hg for G1 and 25 +/- 9 mm Hg for G2 (P = NS). No patient had severe pulmonary insufficiency or required reintervention. CONCLUSIONS: The use of the MTS helped to expedite the procedure providing satisfactory midterm clinical outcomes, similar to those observed with the conventional DBPV technique.     

The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study

BACKGROUND: Lifelong adherence to a strict gluten-free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT-1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae. AIM: To determine the safety and tolerability of 12 mg doses of AT-1001 in coeliac disease subjects challenged with gluten. METHODS: An in-patient, double-blind, randomized placebo-controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy. RESULTS: Compared to placebo, no increase in adverse events occurred in patients exposed to AT-1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group. Interferon-gamma levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT-1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT-1001 group (P = 0.018). CONCLUSIONS: AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.     

Mechanisms of relaxant action of a crude hexane extract of Gnaphalium liebmannii in guinea pig tracheal smooth muscle

We investigated the mechanisms of action of Gnaphalium liebmannii which is used as a folk medicine in México for treating various respiratory diseases such as gripe, fever, asthma, cough, cold, bronchitis, expectorating, and bronchial affections. The tension changes of guinea pig tracheal segments were isometrically recorder on a polygraph. Hexane extract of Gnaphalium liebmannii was the most active relaxant extract (IC(30)=54.23+/-19.79 microg/mL with 99.5+/-3.2 % of relaxation), followed by dichloromethane extract (IC(30)=120.22+/-5.27 microg/mL) and methanol extract (IC(30)=190.25+/-30.02 microg/mL). Hexane extract produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner (pA(2)=-2.4), but did not modify the concentration-response curves for histamine. The relaxant effect of hexane extract of Gnaphalium liebmannii was unaffected by the presence of propranolol (3x10(-6)M) or glibenclamide (10 microM). However hexane extract produced a leftward shifts of the concentration-response curve of forskolin (10(-8) to 10(-3)M), nitroprusside (10(-10) to 10(-6)M), isoproterenol (3x10(-10) to 3x10(-5)M) and aminophylline (10(-11) to 10(-2)M). The above results suggest that Gnaphalium liebmannii induce relaxation of the tracheal muscle, probably via phosphodiesterase inhibition. The bronchodilator effect of Gnaphalium liebmannii might explain in part their traditional use as anti-asthmatic remedy.     

Assessment of PFA-100 system for the measurement of bleeding time in oral surgery

The common diagnostic methods to know primary hemostasis have been classified as invasive, depending on the operator, difficult to reproduce and at times not very reliable. Thus, different systems have been proposed to assess bleeding time, one of them being the PFA-100 device, which we present in this paper. Objective: Compare specificity between the traditional Ivy method with the PFA-100 system to measure bleeding time. Material and method: We obtained a sample of 33 patients between the age of 24-80 years receiving anti-platelet treatment who needed to undergo oral surgery. Bleeding time was obtained by the Ivy method, an INR by an analysis done on the same day and a Coagucheck one hour before surgery as well as measurement of bleeding time with the PFA-100 system. Results: Mean value of bleeding time through the Ivy method was 406.36 sec.. Mean bleeding time with the PFA-100 system for the collagen/epinephrine cartridge was 226.91 sec. and for the collagen/ADP cartridge was 110.27 sec.. All these values were within normality. We observed very high standard deviations with the Ivy method and more regular ones for the PFA-100 system, indicating its greater specificity. We also obtained a large correlation between collagen/epinephrine cartridge and acetylsalicylic acid. Conclusions: We found greater specificity of the analyzer of PFA-100 platelet function for the measurement of bleeding time in relationship with the traditional Ivy method.     

Toward personalized medicine in renal transplantation

Background

The pharmacokinetics of tacrolimus (TRL) are clearly affected by genetic polymorphisms in drug-metabolizing enzymes, which lead to large interindividual differences in dose-response relations. In addition, TRL has a narrow therapeutic index requiring monitoring of blood levels. The objective of the present observational, retrospective study was to associate maintenance TRL doses with various genetic markers seeking to guide optimization of the initial dose.

Methods

Results of DNA samples from 15 kidney transplant patients were correlated retrospectively with clinical information from medical records. Samples were genotyped using PHARMAchip. Association studies were performed with χ² and Pearson tests and by analysis of variance. The study was carried out in accordance with international ethical standards of the Helsinki Declaration and approved by our ethics committee.

Results

Two patient groups were identified to show a difference in TRL dose requirements: a control (0.014-0.10 mg/kg/per day) and an high-dose group (0.14-0.15 mg/kg/per day). The presence of CYP3A5*1 and the null allele in GSTM1 were significantly associated (P = .01 and P = .04) with the need for higher immunosuppressive doses (>0.10 mg/kg/per day). There were no differences in plasma levels of TRL or other clinical variables between the patient groups.

Conclusion

Determination of the CYP3A5 genotype might be used to predict initial TRL requirements, although other genetic variants also provide important information to adjust the drug dose.