Bioactivity of Ceftazidime and Fluconazole Included in Polymethyl Methacrylate Bone Cement for Use in Arthroplasty.

BACKGROUND: The microorganisms that most frequently cause prosthetic joint infection are methicillin-resistant Staphylococcus aureus and gram-negative aerobic bacillus. Studies have documented the efficacy of mixing antibiotics with polymethyl methacrylate, but that of antifungal drugs has not received much attention. The objective of this in vitro study was to characterize the elution profile and bioactivity of ceftazidime and fluconazole when incorporated into bone cement in proportions intended for prophylaxis and treatment of bone infections. METHODS: Antibiotic-loaded bone cement cylinders in a proportion of 1:40 and 4:40 (ratio of grams of antibiotic to grams of cement) were assayed. Drug delivery was investigated in a flow-through dissolution apparatus (SotaxCE7). To assess bioactivity, antibiotic concentrations were simulated in the joint space of 1000 patients. Antibacterial properties were evaluated by counting colony forming units and the inhibition-halo test. RESULTS: The ratio of released ceftazidime and fluconazole was 453% and 648%, respectively, higher when used for treatment proportions than prophylaxis proportions. A bioactivity simulation exercise showed that the efficacy of ceftazidime/fluconazole determined as the amount of drug is released at the active site in the first 3 days after surgery would depend on the sensitivity of the microorganism and would increase substantially after drain removal. The microbiology study showed that biofilm formation by Pseudomonas aeruginosa could be a problem when ceftazidime was used in treatment or prophylaxis proportions. CONCLUSION: Our in vitro findings suggest that ceftazidime and fluconazole can be added into polymethyl methacrylate for the prevention/treatment of infections associated to joint surgery. Their efficacy depends on the sensitivity of the microorganism causing the infection.

Detection of Early Diffuse Myocardial Fibrosis and Inflammation in Chagas Cardiomyopathy with T1 Mapping and Extracellular Volume.

Purpose: To evaluate myocardial T1 mapping and extracellular volume (ECV) parameters in different stages of Chagas cardiomyopathy and determine whether they are predictive of disease severity and prognosis. Materials and Methods: Prospectively enrolled participants (July 2013 to September 2016) underwent cine and late gadolinium enhancement (LGE) cardiac MRI and T1 mapping with a precontrast (native) or postcontrast modified Look-Locker sequence. The native T1 and ECV values were measured among subgroups that were based on disease severity (indeterminate, Chagas cardiomyopathy with preserved ejection fraction [CCpEF], Chagas cardiomyopathy with midrange ejection fraction [CCmrEF], and Chagas cardiomyopathy with reduced ejection fraction [CCrEF]). Cox proportional hazards regression and the Akaike information criterion were used to determine predictors of major cardiovascular events (cardioverter defibrillator implant, heart transplant, or death). Results: In 107 participants (90 participants with Chagas disease [mean age ± SD, 55 years ± 11; 49 men] and 17 age- and sex-matched control participants), the left ventricular (LV) ejection fraction and the extent of focal and diffuse or interstitial fibrosis were correlated with disease severity. Participants with CCmrEF and participants with CCrEF showed significantly higher global native T1 and ECV values than participants in the indeterminate, CCpEF, and control groups (T1: 1072 msec ± 34 and 1073 msec ± 63 vs 1010 msec ± 41, 1005 msec ± 69, and 999 msec ± 46; ECV: 35.5% ± 3.6 and 35.0% ± 5.4 vs 25.3% ± 3.5, 28.2% ± 4.9, and 25.2% ± 2.2; both P < .001). Remote (LGE-negative areas) native T1 and ECV values were also higher (T1: 1056 msec ± 32 and 1071 msec ± 55 vs 1008 msec ± 41, 989 msec ± 96, and 999 msec ± 46; ECV: 30.2% ± 4.7 and 30.8% ± 7.4 vs 25.1% ± 3.5, 25.1% ± 3.7, and 25.0% ± 2.2; both P < .001). Abnormal remote ECV values (>30%) occurred in 12% of participants in the indeterminate group, which increased with disease severity. Nineteen combined outcomes were observed (median follow-up time: 43 months), and a remote native T1 value greater than 1100 msec was independently predictive of combined outcomes (hazard ratio, 12 [95% CI: 4.1, 34.2]; P < .001). Conclusion: Myocardial native T1 and ECV values were correlated with Chagas disease severity and may serve as markers of myocardial involvement in Chagas cardiomyopathy that precede LGE and LV dysfunction.Keywords: MRI, Cardiac, Heart, Imaging Sequences, Chagas Cardiomyopathy Supplemental material is available for this article. © RSNA, 2023.

[Organic pollutant residues of different origins in Navarra]. / Residuos de contaminantes orgánicos de diferentes orígenes en Navarra.

An analysis was made of residues of polychlorobyphenyls and trihalomethanes through GC-ECD and of herbicides through HPLC-PAD in samples proceeding from Navarra. Polychlorobyphenyls were detected (0.30 +/- 0.05 and 0.11 +/- 0.05 microg/l) in two of the 106 water samples analysed. Sixty-six food samples were analysed, and polychlorobyphenyls were only found in 8 samples of trout (dissimilar to dioxins: 21-194 microg/kg of fat; similar to dioxins: 41-139 microg/kg of fat). Of 107 fat samples analysed, polychlorobyphenyls dissimilar to dioxins were detected in two (27 +/- 5 and 30 +/- 5 microg/kg). Out of a total of 94 feed samples analysed, polychlorobyphenyls were detected in all the samples (12) of feed for aquaculture and their raw materials; the concentration of polychlorobyphenyls dissimilar to dioxins varied by an interval of 8-247 microg/kg of fat; polychlorobyphenyls similar to dioxins, between 18 and 107 microg/kg of fat. Contamination by polychlorobyphenyls of the fish from aquaculture could be due to the feed used in these exploitations. The average of trihalomethanes in the waters of the southern zone of Navarra (44 +/- 4 microg/l) was higher than those of the middle zone (16 +/- 1 microg/l) and the mountain zone (12 +/- 1 microg/l). The concentration of 99% of the samples fulfilled the norms on halomethanes. A relation was observed between muddiness and the concentration of trihalomethanes. Herbicide (cianazine) was only detected in one of the 135 samples of water analysed, with a concentration of (0.4 +/- 0.2 microg/l) which exceeded the established limit. The use of confirmation techniques (GC-MS, HPLC-MS/MS) would make it possible to validate these results and to expand the number of compounds analysed.

[Role of intraoperative echo-Doppler color echocardiography in cardiac surgery. Preliminary study]. / Papel de la ecocardiografía intraoperatoria mediante eco-Doppler color en cirugía cardíaca. Estudio preliminar.

Intraoperative echocardiography with Doppler color flow imaging technique can provide the surgeon with an immediate and direct assessment of cardiac anatomy and function. To determine the utility of this recent technique, we have examined 15 patients pre, per, and postoperatively with Doppler color flow imaging. The intraoperative study was performed before and after cardiopulmonary bypass. A sterile transducer was placed directly on the epicardial surface of the heart, and multiple views were recorded. Intraoperative echocardiography with Doppler color flow imaging technique demonstrated excellent correlation with preoperative and postoperative findings, allowing an immediate evaluation of the surgical results. These preliminary results suggest that intraoperative Doppler color flow imaging technique is a valuable adjunct in heart surgery. It is particularly useful in valve repair, and in surgical repair of congenital heart disease.

[Clinical profile and results of transluminal coronary angioplasty in women. Comparison with men]. / Perfil clínico y resultados de la angioplastia coronaria transluminal en la mujer. Comparación con el varón.

To determine if the results of percutaneous transluminal coronary angioplasty are similar in women and in men or any difference between both sexes exists, we have compared 43 clinical and 61 angiographic or procedural variables of 85 consecutive transluminal coronary angioplasties performed in women with 421 similar consecutive procedures in men. Only cigarette smoking was more frequent in men (84 vs 11%, p less than 0.001), being the remaining coronary risk factors more common in women (hypertension 69% vs 37%, p less than 0.001; hypercholesterolemia 46% vs 33%, p less than 0.05, and diabetes mellitus 42% vs 14%, p less than 0.01). In addition, unstable angina was a more frequent indication of coronary angioplasty in women than in men (74% vs 61%, p less than 0.05), whereas coronary angioplasty after intravenous thrombolysis was more frequent in men (12% vs 1%, p less than 0.001). Coronary angioplasty angiographic success (87% vs 91%), and minor (16% vs 10%) or major (5% vs 3%) complications were not statistically different in the two groups. Nevertheless, success of the procedure in the absence of any complication was achieved in a higher percentage (86% vs 76%, p less than 0.05) of men than in their female counterparts. After coronary angioplasty 88% of women had an angiographic follow-up available which yielded a restenosis rate of 41% (vs 32% in men, NS), despite the absence of symptoms in the 89% of these patients in their last visit. In conclusion, we have found that the feminine population subjected to coronary angioplasty have a higher incidence of coronary risks factors and more frequently unstable angina than the masculine group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Color Doppler study of 2 complicated aortic abscesses ruptured into the right ventricle and left atrium]. / Estudio con Doppler en color de 2 abscesos aórticos complicados: rotura a ventrículo derecho y a aurícula izquierda.

This report describes 2 patients with infective endocarditis who subsequently developed aortic abscesses which eventually ruptured, in one case to the right ventricular outflow tract and, in the other, to the left atrium causing, in both patients, severe hemodynamic derangement. The site of communication between the abscesses and the receiving chamber was accurately diagnosed by color flow Doppler imaging which provided more valuable preoperative information than conventional techniques.

[Conventional and color Doppler echocardiography in mitral balloon valvotomy]. / Ecocardiografía-Doppler convencional y color en la valvotomía mitral con balón.

With the aim of assessing the value of conventional echocardiography and Doppler and colour Doppler during and in the follow-up of percutaneous mitral valvotomy we have studied prospectively 100 consecutive patients with 1 (90%), 6 (69%) and 12 (53%) months follow-up. Age was 50 years and 80% were women. The single balloon technique was used in 68%, mitral valve area increased from 0.9 +/- 0.2 to 1.8 +/- 0.3 cm2 and decrease in pulmonary artery pressure was 10 +/- 0.05 mmHg. We found that: 1) percutaneous mitral valvotomy produced and acute and transient decrease in left ventricular ejection fraction (pre 69 +/- 9%, post 61 +/- 10% p less than 0.001; 1 month 70 +/- 10; 2) a severe mitral regurgitation appeared in 4% of patients and 17% of patients had a moderate degree of regurgitation after valvotomy; 3) after valvular dilation an increase in the width of the aliasing greater than 29% predicted a successful procedure (final area greater than 1.5 cm2) with a sensibility 80% and specificity 94%, and 4) colour Doppler detected an atrial septal defect immediately after valvular dilation in 77% of patients, and permitted non invasive follow-up of the left to right shunt. At one year a left to right shunt at the atrial level persisted roughly in 1/3 of patients. We conclude that colour Doppler Echocardiography during percutaneous mitral valvotomy is useful for a rapid assessment of the increase in valve area, the detection and quantification of mitral regurgitation induced by valvular dilation and the follow-up in these patients.

[Effect of the use of echoenhancers on interobserver variability in dobutamine stress echocardiography]. / Influencia de la administración de ecopotenciadores sobre la variabilidad interobservador en la ecocardiografía de estrés con dobutamina.

INTRODUCTION: Dobutamine stress echocardiography is an accurate technique for the noninvasive diagnosis of coronary artery disease. However, interobserver variability is an important limitation of stress echocardiography. Image quality and echocardiographer experience have been described to influence interobserver agreement. AIM: The aim of this study was to determine whether use of contrast agents during dobutamine stress echocardiography improves the agreement between an experienced and a unexperienced observer, and if learning period would be influenced by the use of contrast. METHODS: Two blind observers interpreted all the studies: one experienced echocardiographer (A) and one unexperienced observer (B) in this technique. The contrast agent Levovist/Levograf 2.5 g was administered by two bolus (at rest and at peak stress). In all cases, second harmonic imaging and stress digitalisation packs were used. The kappa test was used to determine interobserver agreement. RESULTS: Fifty-two unselected consecutive studies in 51 patients were analyzed. Twenty-two studies were performed with contrast. The agreement between the experienced and the unexperienced observer was Kappa 0.58 and 0.52, with and without the use of contrast, with no statistically significant difference being archived. CONCLUSIONS: The routine use of contrast provides better although not significant, interobserver agreement. However, this improvement is not sufficient to substitute specific training.

[Isolated ventricular diverticulum in asymptomatic male]. / Divertículo ventricular aislado en varón asintomático.

Ventricular diverticulum are small outpouchings, in the cardiac wall, which are mostly described as a part of malformation syndromes. This finding is infrequent in asymptomatic patients with no pathology in the thoraco abdominal line. The case we present shows a diverticulum in the cardiac apex in a male patient with no cardiological clinic manifestations and with an abnormal electrocardiogram. At present, magnetic resonance is the best diagnostic test, for this kind of malformation, and is also the most reliable in the follow-up of these patients.

[Percutaneous mitral valvulotomy using the Inoue balloon technique]. / Valvulotomía mitral percutánea con la técnica de Inoue.

We have reviewed our initial experience with percutaneous mitral valvulotomy (PMV) in 29 consecutive patients with mitral stenosis using the Inoue mono-balloon technique. In all cases, the venous transeptal anterograde approach was used. Age was 49.5 +/- 12.5 years (range 21-78) and only 5 (17%) patients were male. Clinical status was as follows: 15 patients were in NYHA class II, 13 NYHA class III and one in NYHA class IV. Atrial fibrillation was present in 15 (52%) patients and 16 (55%) were on coumarin. An echocardiographic score was employed to assess mitral valve anatomy, parameters including degree of thickening, mobility, calcification and subvalvular involvement were scored independently from 1 to 4. The echocardiographic score so determined was 7.72 +/- 2.1 for the entire group. Ten patients presented mild (+) mitral regurgitation prior to PMV. The mean duration of PMV was 76.2 +/- 29.6 minutes. In only one patient an inadequate positioning of the balloon prevented dilatation of the valve whereas the remaining 28 patients had their valves successfully dilated. Mitral valve area, by means of both Gorlin and Doppler (pressure half time) methods, increased in all cases: from 0.95 +/- 0.17 cm2 to 1.92 +/- 0.31 cm2 (p less than 0.001) and from 0.97 +/- 0.22 to 1.84 +/- 0.33 cm2 (p less than 0.001), respectively. Mitral regurgitation increased angiographically in more than 1 degree only in 1 patient, but no other cardiac or vascular complication occurred. Thus, in our experience PMV with the Inoue mono-balloon catheter is a safe and effective method for dilating mitral valve stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Usefulness of contrast echocardiography with harmonic imaging in a patient with hypertrophic cardiomyopathy and midventricular obstruction]. / Utilidad de la ecocardiografía de contraste con segundo armónico en un paciente con miocardiopatía hipertrófica y obstrucción mesoventricular.

Echocardiography is routinely used for the evaluation of cardiac function. Definition of the endocardial border is essential for the assessment of global and regional left ventricular contractility. This is sometimes difficult due to an inadequate acoustic window. New echocardiographic techniques may be useful to accurate and noninvasively diagnose certain conditions which may otherwise remain undiagnosed with traditional techniques. We present a case of a patient diagnosed with segmental wall motion abnormalities (lateral and apical hypokinesis) by conventional echocardiography. The use of harmonic imaging with contrast changed the initial diagnosis and the patient was diagnosed with severe hypertrophic cardiomyopathy with midventricular obstruction, without segmental wall motion abnormalities.

[Coronary angioplasty: experience at the University Hospital of Madrid]. / Angioplastia coronaria: experiencia en el Hospital Universitario de Madrid.

The results of 963 consecutive coronary angioplasties, with 1.135 lesions attempted in 816 patients, were prospectively analyzed. Initial angiographic success (residual stenosis less than 50%) was achieved in 1.017 lesions (89.6%), and final success was obtained in 838/963 procedures (87%). Major complications included: emergency surgery in 4 cases (0.4%), acute myocardial infarction in 28 (2.9%), and death during hospitalization in nine (0.9%). Surgical stand-by was required only for cases with vital risk should the attempted vessel occlude. This criteria was present in 230 (23.8%) angioplasties. Coronary angioplasty was performed during the diagnostic procedure in 300 (31.1%) case, with final success in 264 (88%) of them. A exercise test was achieved before the procedure in 419 (50%) successful angioplasties and in 246 (58.7%) of them it was abnormal because of angina (with or without ST depression). After procedure, exercise could be performed in 780 cases (93%), and the result remained unchanged in only 44 (5.6%) (p less than 0.01). At discharge 780 (93%) patients with final success considered themselves clinically improved. In our experience, coronary angioplasty is a good myocardial revascularization technique, with high success, low rate of major complications, and that provides a good clinical outcome. Surgical stand-by may be unnecessary in prost of angioplasty procedures if patients selection is carefully done, also, this approach makes it possible to perform angioplasty at time of diagnostic catheterization.

[Transient paradoxical embolism. Importance of early ultrasonography diagnosis]. / Embolia paradójica en tránsito. Importancia del diagnóstico ecocardiográfico precoz.

The paradoxical embolism or the crossing of an embolism through a permeable foramen ovale is considered to be a rare mechanism of cerebral embolism although its real frequency is unknown. Reports demonstrating the embolism during its crossing through cardiac cavities are scarce. Two cases of moving paradoxical embolism are presented. In the first, an infarction of the superior branch of the left middle cerebral artery was produced during the course of deep vein thrombosis and pulmonary thromboembolism with transesophageal echocardiography demonstrating the crossing of the embolism through the foramen ovale. Surgery performed 12 days later did not discover the auricular thrombus. In the second case, a mass was discovered in the right auricle with a permeable foramen ovale during the course of a left middle cerebral artery infarction and a large auricular thrombus was demonstrated in surgery. The diagnostic usefulness of early transsesophageal echocardiography in the diagnosis of moving paradoxal embolism is discussed.

In vitro evaluation of extemporaneously compounded immediate-release capsules with premixed excipients, based on the biopharmaceutics classification system (BCS) of the drugs.

Hard-capsule compounding plays an essential role in drug delivery for pharmaceutical application. Versatile and easy to use, capsules represent a popular dosage form for patients. Nevertheless, bioavailability of the drugs compounded in hard capsules is not always optimized and choosing the appropriate excipients is a key factor to improve the dissolution kinetics of active pharmaceutical ingredients. The Biopharmaceutical Classification System, which categorizes drugs regarding their solubility and permeability, is a unique tool which can be used to select the most compatible excipients for a particular drug when compounding immediate-release capsules. The aim of this study was to evaluate the efficiency of premixed excipient blends called CapsuBlend Excipients, based on the Biopharmaceutical Classification System concept, for drug dissolution rate and absorption enhancement. Drug assay and dissolution profiles were studied for three batches of metronidazole 250-mg, theophylline 100-mg, and levocarnitine 250-mg capsules, each respectively representing a highly soluble, poorly soluble, and hygroscopic drug. Methods followed the specifications set forth in the United States Pharmacopeia. Assay results demonstrated that each batch of metronidazole 250 mg, theophylline 100 mg, and levocarnitine 250 mg contained not less than 90.0% of and not more than 110.0% of the labeled amount of drug, which is in accordance with the United States Pharmacopeia requirements. Moreover, dissolution profile results for the aforementioned capsules depicted dissolution values meeting the Pharmacopeial criteria of acceptance. These results reinforce the fact that the Biopharmaceutical Classification System concept represents a valuable guideline for formulation chemists or pharmacists to assist them for capsule compounding. To ensure a high level of efficiency of compounded capsules, premixed excipient blends, carefully developed by taking into consideration the solubility and permeability of a drug, represent a significant formulation advantage to improve the dissolution of active pharmaceutical ingredients.