New europium-doped carbon nanoparticles showing long-lifetime photoluminescence: Synthesis, characterization and application to the determination of tetracycline in waters.

The growing appearance of antibiotic-resistant strains of microorganisms originated from the widespread use and ubiquitous presence of such drugs is a major concern in the world. The development of methodologies able to detect such substances at low concentration in real water samples is mandatory to overcome this problem. Europium(III) is known to form complexes with tetracycline (TC) with photoluminescent characteristics useful for TC determination. In the present work, we synthesized for the first time carbon nanoparticles (CN) showing delayed photoluminescence using a Europium(III) doping synthesis. The new material (PCNEu) was characterized both morphologically and spectroscopically, showing an analytical photoluminescent signal in presence of TC, arising from the 5D0→7F2 transition of europium, one hundred times higher than that of the europium salt alone in presence of the antibiotic. This enhancement is a consequence of the amplifying effect exerted by nanoparticle structure itself, leading to an efficient synergistic "antenna effect" in the system PCNEu - TC. The analytical signal is affected both by pH and the nature of the buffer used, and it allows the detection of tetracycline in waters with a limit of detection of 2.18 nM and recoveries between 90 and 110%. The analytical performance of the developed methodology enables having lower limits of detection than other luminescent and chemiluminescent reported methodologies.

Controlled release of nafcillin using biocompatible "dummy" molecularly imprinted sol-gel nanospheres.

Different silicon-based xero-gel molecularly imprinted spheres in the nano boundary range with recognition capabilities for nafcillin have been synthesised, using tetraethylorthosilicate (TEOS) and (3- aminopropyl) triethoxysilane (APTEOS) as precursors. Imprinting has been achieved using both nafcillin (NAF) or structural analogous 'dummies' such as (+)-6-aminopenicillenic acid (APA), or ampicillin ((+)-6- aminobenzylpenicillin)sodium salt (AMP). Materials were fully characterized using ATR-FTIR, (29)Si solidstate NMR, TGA, TEM and BET. Adsorption isotherms for all the materials fit with a continuous Freundlich model with correlation coefficients better than 0.988 and mean affinity constants between 10(5) and 10(6) L·mol(-1). The use of 'dummies' as well as the template itself in the imprinting process resulted in materials with different release speed. Combinations of these materials allow designing mixtures with a continuous, controlled and constant release longer than four days. Thus, the non-imprinted and the AMP-imprinted material have a rapid release during the first five hours, nafcillin and APA imprinted ones release antibiotic mainly after a latency-period of 24 hours.

Molecularly imprinted silica-silver nanowires for tryptophan recognition.

We report on silver nanowires (AgNWs) coated with molecularly imprinted silica (MIP SiO2) for recognition of tryptophan (Trp). The use of AgNWs as a template confers an imprinted material with adequate mechanical strength and with a capability of recognizing Trp due to its nanomorphology when compared to spherical microparticles with a similar surface-to-volume ratio. Studies on adsorption isotherms showed the MIP-SiO2-AgNWs to exhibit homogeneous affinity sites with narrow affinity distribution. This suggests that the synthesized material behaves as a 1D nanomaterial with a large area and small thickness with very similar affinity sites. Trp release from MIP-SiO2-AgNWs was demonstrated to be dominated by the diffusion rate of Trp as controlled by the specific interactions with the imprinted silica shell. Considering these results and the lack of toxicity of silica sol-gel materials, the material offers potential in the field of drug or pharmaceutical controlled delivery, but also in optoelectronic devices, electrodes and sensors.

Assessment of molecularly imprinted sol-gel materials for selective room temperature phosphorescence recognition of nafcillin.

Sol-gel imprinted materials were prepared against nafcillin, a semisynthetic beta-lactamic antibiotic employed in the treatment of serious infections caused by penicillinase-producing staphylococci. Two approaches were addressed for preparation of the imprinted materials and the controls: as conventional monoliths, which were ground and sieved to a desired particle size for rebinding analysis, and as films on supporting glass slides. The specific binding sites that are created during the imprinting process are analyzed via selective room temperature phosphorescence (RTP) (sol-gel films) measurements as well as via competitive room temperature phosphorescence ligand assay. Results demonstrated the importance of the physical configuration of the imprinted material for minimizing non-specific binding. The close similarities between the structures of different beta-lactamic antibiotics made it possible to interpret the roles of the template structure on specific molecular recognition. In this article, we introduce the use of room temperature phosphorescence as selective transduction method for the template. The imprinted sol-gel films displayed enhanced specific binding characteristics respect to the monolithic sol-gel and can be envisaged for the use as recognition matrices for the screening and rapid selection of antibiotics from a combinatorial library or for the rapid control of nafcillin in biological samples (e.g. milk, serum, urine).

Ralitrexed (Tomudex) or Nordic-FLv regimen in metastatic colorectal cancer: a randomized phase II study focusing on quality of life, patients' preferences and health economics.

Raltitrexed (Tomudex) is proven effective in metastatic colorectal cancer. Between 1998-2000, 25 patients were included in a randomized phase II study comparing raltitrexed (13 patients) and the Nordic FLv regimen (12 patients). 23 patients were evaluable for response. The overall response rate was 2/12 (1 CR, 1 PR) in the raltitrexed arm and 1/11 (1 CR) in the Nordic FLv arm, respectively. There was no difference in overall survival (raltitrexed--14.7 months, Nordic FLv--15.4 months). 23 patients were evaluable for Quality of Life (QoL) analysis. 23/25 and 17/21 questionnaires (EORTC QLQ C-30) were returned at baseline and first evaluation. Raltitrexed tended to be the most toxic regimen, when looking at nausea and vomiting, appetite loss, diarrhea and global QoL. However, most patients (65%) recommended the raltitrexed treatment schedule. The total treatment cost was equal in both arms (about 6,800 EURO/patient) and the hospital/hospital hotel stay costs accounted for more than half of it.

Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study.

PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.

Ventricular tachycardia in Chagas' disease.

This study examined the usefulness of the electrophysiologic approach for selecting antiarrhythmic drug therapy to improve survival in patients with ventricular tachycardia (VT) and Chagas' disease. A total of 71 consecutive chagasic patients undergoing treatment and evaluation of VT were analyzed. Programmed electrical stimulation (PES) was performed in 45 patients, sustained VT was induced in 18 of these 45 (40%); nonsustained VT was induced in 17 (38%), and in 10 patients (22%) VT was not induced at all. An average of 3 drugs per patient were tested, including mexiletine, flecainide and propafenone. At least 1 effective drug preventing VT induction was identified in 13 of 18 patients with induced sustained VT, whose outcome resulted in 2 nonsudden but cardiac deaths (15%). Eight patients received no drug therapy because the induced arrhythmia was asymptomatic nonsustained VT; none of these died. The remaining 24 patients from the PES group were empirically treated with amiodarone; 7 died (4 suddenly) during follow-up (29%). A group of 26 patients (non-PES group) did not undergo electrophysiologic evaluation. In these patients, the therapy chosen was amiodarone alone or associated with mexiletine, and the incidence of death was 7 of 26 patients (27%), 3 suddenly (p less than 0.05 at 10-year survival and p = not significant at 5-year survival). It is concluded that the electrophysiologic approach improves survival in this study population, but only 29% were eligible for guided therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of the ajmaline test in patients with latent bundle branch block.

Twelve patients were studied with intermittent bundle branch block whose conduction disturbance disappeared completely and could no longer be recorded even after provoked changes in heart rate. Premature atrial stimulation and atrial pacing at rapid rates were performed in nine patients; in none of these nine were these procedures able to evoke the complete bundle branch block pattern that all patients exhibited before the spontaneous normalization of conduction. In marked contrast, the administration of ajmaline (1 mg/kg body weight, intravenously in 90 seconds) caused the bundle branch block pattern to reappear in 10 (83.3 percent) of the 12 patients 30 to 120 seconds after the end of the injection, and in 11 patients (91.6 percent) when additional atrial stimulation was performed in 1 of the 2 "failures." This pharmacologic test was much more rapid and simple than electrophysiologic testing and it was noninvasive. Results of this study suggest that some form of subclinical fascicular injury was present (or had persisted) at a time when intraventricular conduction was persistently normal even though no significant physiologic alteration could be demonstrated by the atrial stimulation techniques. The ajmaline test may become a valuable tool for uncovering cases of latent bundle branch block and furthering our knowledge of the early natural history of intraventricular block.

Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.