Pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of ceftazidime/avibactam administered by continuous infusion in patients with MDR Gram-negative bacterial infections.

BACKGROUND: Therapeutic drug monitoring (TDM) of ß-lactams in critically ill patients has been correlated with better clinical outcomes. Evidence on TDM of newer ß-lactams such as ceftazidime/avibactam administered by continuous infusion (CI) is very limited. OBJECTIVES: To describe our experience with TDM of ceftazidime/avibactam and pharmacokinetic/pharmacodynamic (PK/PD) target attainment in patients with MDR bacterial infections. Clinical outcomes of ceftazidime/avibactam administered by CI were also assessed. METHODS: Patients treated with ceftazidime/avibactam administered by CI and undergoing TDM of ceftazidime plasma concentrations were included. Blood samples were obtained as part of the TDM program. The PK/PD therapeutic target of ceftazidime/avibactam was defined as 100%fT > 4 × MIC of the causative pathogen, and 100%fT > 10 × MIC was considered overexposure. Dose changes were made according to the TDM results. RESULTS: Thirty-one patients were included. Ceftazidime/avibactam total daily doses ranged from 1 g/0.25 g to 6 g/1.5 g. Twenty-six patients (83.9%) achieved a 100%fT > 4 × MIC, 15 (48.4%) of which were overexposed (100%fT > 10 × MIC). Dose reduction was suggested in 16/28 (57.1%) patients and dose maintenance in 12/28 (42.9%). Overall clinical cure was observed in 21 (67.7%) patients, and 18 of these (85.7%) achieved a 100%fT > 4 × MIC. CONCLUSIONS: Administering ceftazidime/avibactam by CI enabled the desired PK/PD target to be achieved in a large proportion of patients, even at lower doses than those recommended for a 2 h extended infusion. We suggest that the use of CI with TDM may be a useful tool for reducing initial doses, which could help to reduce antimicrobial-related adverse effects and treatment costs.

Contribution of bone conduction click-evoked auditory brainstem responses to diagnosis of hearing loss in infants in France.

INTRODUCTION: Neonatal hearing screening in France involves confirmation by a childhood hearing expert centre in case of suspected hearing loss. Although click-evoked air-conduction auditory brainstem responses (AC-ABR) are the gold standard in France, there are no guidelines for bone-conduction ABRs (BC-ABR). The present study assessed the interest of associating click-evoked BC- and AC-ABRs for diagnostic confirmation in neonatal hearing screening. MATERIALS AND METHODS: A retrospective study included 59 infant ears with conductive hearing loss referred to the centre of Lyon, France. Objective hearing thresholds were compared between click-evoked BC- and AC-ABRs on a method previously validated in a normal-hearing population. RESULTS: There was a significant difference in mean threshold between AC-ABR (53.27±1.189 dBnHL) and BC-ABR (28.1±0.935 dBnHL) (P<0.001). AC thresholds ranged from 40 to 60 dBnHL while BC thresholds exceeded 40 dBnHL in only 9 ears. CONCLUSION: Using BC-ABRs could reduce the false-positive rate in neonatal bilateral permanent hearing loss screening, in complement to AC-ABRs using the same stimulus. Click-evoked BC-ABR could be contributive whenever conductive hearing loss is suspected, in complement to AC-ABR, without unreasonably increasing examination time.

Disaccharide anthocyanin delphinidin 3-O-sambubioside from Hibiscus sabdariffa L.: Candida antarctica lipase B-catalyzed fatty acid acylation and study of its color properties.

Enzymatic lipophilization is an important process to extend the use of anthocyanins in lipidic media. In this work delphinidin 3-O-sambubioside (Dp3sam) isolated from Hibiscus sabdariffa L. flower was esterified with octanoic acid using Candida antarctica lipase B. The physical-chemical properties of the new lipophilic pigment were studied by UV-vis spectroscopy. Dp3sam with chloride, acetate and formate as counter ions were employed to study the lipophilization reaction. The hydrolysis of the reagent was avoided with a formate counter ion and the expected product was achieved with a noteworthy change of solubility. 1D and 2D NMR characterization of Dp3sam-C8 confirmed that the lipophilization took place at the primary alcohol of the glucoside moiety. Overall, the Dp3sam-C8 ester presents a stabilization of the quinoidal base (blue color) at neutral or moderate alkaline pH, which foresees a potential use of this pigment as a broad kind of industries on lipo-soluble formulations.

Functional aptitude of hake minces with added TMAO-demethylase inhibitors during frozen storage.

The ability of compounds of natural origin (black, white, red, and green tea extracts, phytic acid) to inhibit TMAO-demethylase enzyme was assayed. Black tea and phytic acid exerted the highest inhibiting activities, similar to the already known inhibitor sodium citrate. Hake minces incorporating these three compounds were prepared and stored frozen (150 days, -12 °C). TMAO-demethylase enzyme was partially inhibited (lower enzyme activity, reduction of formaldehyde accumulation). The study of physicochemical properties of the minces (salt-soluble proteins, water holding capacity, structural water associated with myofibrils) pointed to evident protein aggregation and loss of functionality when phytic acid was added, whereas black tea and sodium citrate did not have a negative effect. Consequently, the salt-ground mince with phytic acid showed worse viscoelastic properties than the others. In conclusion, black tea polyphenols and sodium citrate can be used as additives to inhibit TMAO-demethylase enzyme during frozen storage of fish minces.

Physical characteristics of nano-Hydroxyapatite Pickering-emulsions and their adjuvant activity on the antibody response towards the Bothros asper snake venom.

Emulsions are crucial in the treatment of snake bites to bust the antibody response of the inmunogen. The widely used Freund's emulsion typically combines 50/50 water-oil (W/O) phase. However, its use is limited because it is associated with tissue damage. We formulated and characterized a Pickering Emulsion 70/30 (W/O) that uses a chemically modified hydrophobic hydroxyapatite as surfactant. This Pickering emulsion has similar rheologic behavior to Freund's emulsion 50/50, but with lower oil and surfactant concentration. Evaluation of cell recruitment, antibody response and adhering tissue in mice immunized with B. asper of Pacific venom and treated with Freund's and Pickering 70/30 emulsions resulted in similar adjuvant activity (only 18% lower in Pickering 70/30 emulsion). However, Pickering 70/30 emulsions minimized negative side effects in the host animals and showed better ease of flow that favors injection of the host. Our results open up room for optimization and improvement of Pickering emulsion based on modified nanoparticles for medical applications.

Ortogeriatría: primer registro multicéntrico autonómico de fracturas de cadera en Castilla y León (España) / Orthogeriatrics: The First multicentre regional register of hip fractures in Castilla y León (Spain)

Objetivo: El objetivo de este trabajo es describir las características de los pacientes con fractura de cadera en los hospitales públicos de Castilla y León recogidos durante un periodo de tiempo de 3 meses (noviembre del 2014 y octubre y noviembre del 2015). Material y método: El grupo de trabajo de Ortogeriatría de Castilla y León elabora un registro común para recoger datos de las fracturas de cadera. Se incluyen mayores de 74 años ingresados por fractura de cadera, en 13 hospitales públicos de la comunidad, los meses de noviembre del 2014 y octubre-noviembre del 2015. Es un estudio multicéntrico, prospectivo y observacional en el que se recogieron variables clínicas, funcionales, sociales y mortalidad intrahospitalaria. Resultados: Se analizaron 776 pacientes, con una edad media de 86,6±6 años. La demora quirúrgica fue de 4±2,8 días y la estancia media hospitalaria de 10±4,7 días. El riesgo anestésico fue ASA 3±0,6. El 66,5% de los pacientes tuvieron complicaciones médicas intrahospitalarias y precisaron transfusión el 55,5%. Fallecieron durante la hospitalización un 4,6%. La estancia media prequirúrgica se relacionó con la estancia global, con p<0,001. Conclusiones: Los registros de fractura de cadera son una herramienta esencial para evaluar el proceso y mejorar la calidad asistencial de estos pacientes. Este es el primer registro multicéntrico de fracturas de cadera en ancianos realizado en una región de España y puede ser un buen precedente de referencia ante el futuro registro nacional (AU)

Objective: The objective of this study is to describe the characteristics of the patients with hip fracture admitted to the Public Hospitals of Castilla y León during three monthly periods (November 2014, and October and November 2015). Material and method: The Castilla y León orthogeriatrics work group created a common register to collect data on hip fractures. The study included patients 75 years-old and over hospitalised with hip fractures in the 13 public hospitals in the community during November 2014, and October and November 2015. A multicentre, prospective, and observational study was conducted, in which clinical, functional, and social variables, as well as in-hospital mortality, were collected. Results: The analysis included data from a total of 776 patients with a mean age of 86 (±6) years. The surgical delay was 4±2.8 days, and the mean hospital stay was 10±4.7 days. The anaesthesia risk was ASA 3±0.6. Around two-thirds (66.5%) of the patients had medical complications while in hospital, and 55.5% required a transfusion. In-hospital mortality was 4.6%. The mean pre-surgical stay was related to the overall stay: P<.001. Conclusions: Hip fracture registers are an essential tool for evaluating the process and for improving the treatment quality of these patients. This is the first multicentre register of hip fracture in the elderly created in a Spanish region, and could be a good precedent reference for a future national register (AU)

Chitooligosaccharides as novel ingredients of fermented foods.

Chitooligosaccharides (COSs) have been clinically evaluated for their immunostimulating effects after oral intake. Similar to dietary supplements, prebiotics and biopreservatives, these water-soluble bioactives are easily incorporated into dairy products and beverages. Notwithstanding, the use of COS in fermented foods would be limited by its antimicrobial properties. In order to study the interaction with yoghurts as a model of fermented food, the effects of COS on chemical composition, viability, morphology and metabolism of lactic acid bacteria, fatty acid profiles and conjugated linoleic acid (CLA) were assessed over 28 days and after chemical digestion. There were no significant differences between the nutritional composition of controls and yoghurts supplemented with concentrations up to 0.1% w/w of COS. However, the acidification of milk decreased at 0.5% (p < 0.05) and the formation of yoghurt failed at 3.0%, without affecting viable counts. Lipid hydrolysis of yoghurts supplemented with 0.1% COS was not affected by chemical digestion. No significant differences were found between CLA percentages of controls and supplemented yoghurts after digestion. Although the nutritional composition, fatty acids and viable counts were not significantly modified after COS supplementation, the present study shows that COS diminishes bacterial acidification at concentrations higher than 0.1%, thus limiting the amounts that could be added to yoghurt.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

INTRODUCTION: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. METHODS AND ANALYSIS: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. ETHICS AND DISSEMINATION: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. TRIAL REGISTRATION NUMBER: NCT01898338.

Tuberculosis in a cohort of HIV-positive patients: epidemiology, clinical practice and treatment outcomes.

OBJECTIVE: To describe tuberculosis (TB) incidence, risk factors, clinical presentation, disease management and outcomes in human immunodeficiency virus (HIV) infected patients from the CoRIS cohort, Spain, 2004-2010. DESIGN: Open multicentre cohort of antiretroviral treatment (ART) naïve patients at entry. Incidence and risk factors were evaluated using multivariate Poisson regression. RESULTS: Among 6811 patients, 271 were eligible for the study and 198 for the estimation of the incidence rate; TB incidence ranged from 12.1 to 14.1/1000 person-years. TB was associated with low education level (rate ratio [RR] 2.65, 95%CI 1.73-4.07), being sub-Saharan African (RR 3.14, 95%CI 1.81-5.45), heterosexual (RR 2.01, 95%CI 1.22-3.29) or an injecting drug user (RR 2.11, 95%CI 1.20-3.69), not undergoing ART (RR 3.33, 95%CI 2.22-4.76), CD4 <200 cells/mm(3) (RR 5.20, 95%CI 3.25-8.33) and log-viral load of 4-5 (RR 5.44, 95%CI 3.28-9.02) or >5 (RR 13.10, 95%CI 8.27-20.76). Overall, 87% were new cases and 13% were previously treated cases; 175 (65%) were bacteriologically confirmed. Drug susceptibility testing was performed in 146 (83%) patients: resistance to first-line drugs was 11.1% in new and 36.4% in previously treated cases. Standard anti-tuberculosis treatment with four or three drugs was prescribed in respectively 55% and 36% of cases. Treatment default was 11%, and was higher among previously treated cases; 80% received ART during anti-tuberculosis treatment, 80% of new and 50% of previously treated cases were cured or completed treatment, and 18 (6.6%) died. CONCLUSION: TB incidence in HIV-infected patients remains high. Interventions should include early HIV diagnosis and access to ART, enhanced bacteriological confirmation, wider use of four-drug regimens and reduction in treatment default.

Improving ex vivo skin permeation of non-steroidal anti-inflammatory drugs: enhancing extemporaneous transformation of liposomes into planar lipid bilayers.

Transdermal delivery of active principles is a versatile method widely used in medicine. The main drawback for the transdermal route, however, is the low efficiency achieved in the absorption of many drugs, mostly due to the complexity of the skin barrier. To improve drug delivery through the skin, we prepared and characterized liposomes loaded with ibuprofen and designed pharmaceutical formulations based on the extemporaneous addition of penetration enhancer (PE) surfactants. Afterwards, permeation and release studies were carried out. According to the permeation studies, the ibuprofen liposomal formulation supplemented with PEs exhibited similar therapeutic effects, but at lower doses (20%) comparing with a commercial formulation used as a reference. Atomic force microscopy (AFM) was used to investigate the effect caused by PEs on the adsorption mechanism of liposomal formulations onto the skin. Non-fused liposomes, bilayers and multilayered lipid structures were observed. The transformation of vesicles into planar structures is proposed as a possible rationale for explaining the lower doses required when a liposome formulation is supplemented with surfactant PEs.

Melanomas cutáneos de cabeza y cuello / Cutaneous melanoma of the head and neck

Se realiza una revisión retrospectiva de 20 pacientes diagnosticados de melanomas cutáneos de cabeza y cuello tratados entre 1991 y 2005. Los avances en las técnicas diagnósticas y en el tratamiento han tenido un impacto obvio en los resultados de los melanomas cutáneos. En estadios tempranos se realiza una resección quirúrgica completa. Los márgenes de resección están determinados por la extensión superficial y en profundidad. Cuando la enfermedad se diagnostica en un estadio avanzado es necesario el estudio de las metástasis regionales y a distancia. El tratamiento complementario podría estar indicado cuando existe afectación regional

The clinical records of 20 patients with the diagnosis of cutaneous melanoma of the head and neck treated between 1991 and 2005 were retrospectively reviewed. Advances in diagnostic techniques and treatment have had obvious impact on outcomes in cutaneous melanoma. Cutaneous melanoma of the head of neck is treated with complete surgical resection in early stage disease. Resection margins are determined by the size and depth. Evaluation for regional and distant metastatic disease is necessary in advanced stage disease. Adjuvant therapy may be indicated in regional nodal disease

Multi-technique characterization of a nuclear bomb particle from the Palomares accident.

A January 1966 accident dispersed Pu and other nuclear bomb materials in the vicinity of Palomares, a village in southeastern Spain. Radioactive particles were identified in a soil sample collected in 1998 and analytical results obtained from one of the isolated particles are presented here. Isolation of the particle was performed using gamma-ray spectrometry and imaging plates. Scanning electron microscopy with X-ray microanalysis revealed the presence of U and Pu as well as Pb and Fe in the particle of approximately 10microm diameter. Radioisotopes of U, Pu, and Am were quantified using radiometric methods, inductively coupled plasma mass spectrometry and secondary ion mass spectrometry. The elevated (235)U/(238)U atom ratio indicates enriched U, and the Pu atom ratios are consistent with weapons-grade material. This work demonstrates that the analysis of individual particles provides information not available through bulk sample analysis.

Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers.

RATIONALE: Ayahuasca is a South American psychoactive beverage that contains the naturally occurring psychedelic agent N,N-dimethyltryptamine (DMT). This "tea" has been used for centuries in religious and medicinal contexts in the rain forest areas of South America and is presently gaining the attention of psychedelic users in North America and Europe. OBJECTIVES: In the present study, the psychological effects and tolerability of ayvahuasca were assessed. METHODS: Three increasing doses of encapsulated freeze-dried ayahuasca (0.5, 0.75, and 1.0 mg DMT/kg body weight) were administered to six healthy male volunteers with prior experience in the use of this tea, in a single-blind crossover placebo-controlled clinical trial. RESULTS: Ayahuasca produced significant dose-dependent increases in five of the six subscales of the Hallucinogen Rating Scale, in the LSD, MBG, and A scales of the Addiction Research Center Inventory, and in the "liking", "good effects" and "high" visual analogue scales. Psychological effects were first noted after 30-60 min, peaked between 60-120 min, and were resolved by 240 min. The tea was well tolerated from a cardiovascular point of view, with a trend toward increase for systolic blood pressure. Modified physical sensations and nausea were the most frequently reported somatic-dysphoric effects. The overall experience was regarded as pleasant and satisfactory by five of the six volunteers, while one volunteer experienced an intensely dysphoric reaction with transient disorientation and anxiety at the medium dose and voluntarily withdrew from the study. CONCLUSIONS: Ayahuasca can be described as inducing changes in the perceptual, affective, cognitive, and somatic spheres, with a combination of stimulatory and visual psychoactive effects of longer duration and milder intensity than those previously reported for intravenously administered DMT.

[Isolated primary hyperaldosteronism caused by adrenocortical carcinoma]. / Hiperaldosteronismo primario aislado causado por carcinoma córtico-suprarrenal.

OBJECTIVE: To report a case of adrenocortical carcinoma and primary aldosteronism as the sole endocrine manifestation. METHODS/RESULTS: A 39-year-old male with adrenocortical carcinoma and primary aldosteronism is presented. Following complete hormonal and radiological evaluation, right adrenalectomy and nephrectomy were performed (pT2pN0M0, stage II). Blood pressure, serum potassium and aldosterone levels returned to normal. The patient received adjuvant therapy with carboplatin and etoposide. After 15 months' disease-free interval, lung metastasis was diagnosed, without evidence of local recurrence until 5 months later, when hypertension and primary hyperaldosteronism reappeared. There were no other endocrine disorders. Treatment with spironolactone, 5-FU and adriamycin was instituted with no tumor response and the patient died 3 years later from complications of endobronchial metastasis. CONCLUSION: Adrenocortical carcinoma with isolated primary hyperaldosteronism is uncommon and consequently there is no wide experience in regard to its diagnosis and treatment. Although randomized studies are not available, adjuvant therapy using other agents instead of mitotane (o,p-DDD), such as the combination of cisplatin and etoposide (VP-16), seems reasonable in the locally advanced stages. Mitotane may be useful when hypercortisolism is present, but its efficacy as an antitumor agent has been controversial.

Gastric antisecretory and antiulcer activities of an ethanolic extract of Bidens pilosa L. var. radiata Schult. Bip.

Bidens pilosa var. radiata Schult. Bip. is used in folk medicine to treat stomach disorders including peptic ulcers. The ethanolic extract (0.5-2 g/kg) decreased the gastric juice volume, acid secretion, as well as pepsin secretion in pylorus ligated rats. B. pilosa extract showed antiulcer activity against indomethacin-induced gastric lesions. The extract effectively inhibited gastric haemorrhagic lesions induced by ethanol, and with an effective dose of 2 g/kg being more potent than sucralfate (400 mg/kg). In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. These results indicate that B. pilosa ethanolic extract exerts a cytoprotective effect in addition to its gastric antisecretory activity that could be due, partly at least, to the presence of flavonoids of which quercetin was identified by HPLC.

Characterization of allergens from Trisetum paniceum pollen: an important aeroallergen in Mediterranean continental climatic areas.

BACKGROUND: Trisetum paniceum is a grass plant which is characteristic of a Mediterranean continental climate and has been described as one of the major causes of type I allergy in the Madrid region. OBJECTIVES: To identify and characterize the allergens of Trisetum paniceum pollen. METHODS: Allergenic extracts were prepared by 24 h incubation of pollens in a buffered solution. Proteins were analysed by a new two-dimensional system in which agarose plates were used for isoelectric focusing. Two-dimensionally resolved proteins were electrically transferred to Immobilon membranes and the allergens immunochemically detected. Proteins from six grass pollens were bound to a membrane and incubated with a pool of serum from grass-pollen-sensitized patients. The bound IgE antibodies were then eluted and used to identify the proteins of Trisetum paniceum pollen that allergenically crossreact with allergens from other pollen grasses. RESULTS: Relative to total protein content, Trisetum paniceum pollen had a high proportion of reactive proteins. On the basis of their molecular characteristics, allergens could be classified as group 1, 2, 4 and 5 components yet included an atypical proportion of basic components. All identified allergens were crossreactive with allergens from the remaining grass pollens studied. CONCLUSIONS: Trisetum paniceum pollen contains a high proportion of allergens and these include a group of basic proteins which are not detected in other phylogenetically related pollens and could be of allergological interest.

Targeting aequorin and green fluorescent protein to intracellular organelles.

Two proteins of Aequorea victoria were molecularly engineered and produced in mammalian cells, in order to serve as specific reporters of subcellular microenvironments. Aequorin (AEQ), a Ca(2+)-sensitive photoprotein, was successfully targeted to three intracellular locations: cytosol, nucleus and mitochondria. The recombinant apoprotein, reconstituted into active AEQ by the addition of the prosthetic group to the culture medium, allows the direct measurement of [Ca2+] within those compartments, thus directly addressing questions of large biological interest. The same approach was utilized for the green fluorescent protein (GFP) for specific labelling, in vivo, of the various subcellular structures. GFP was targeted to mitochondria: the recombinant protein, strongly fluorescent in a highly reducing environment, provides a powerful tool for visualizing these organelles in living cells, and may represent the prototype of a new family of intracellularly targeted fluorescent probes.

[Electrocardiographic diagnosis and acute treatment of atrial fibrillation and flutter episodes]. / Diagnóstico electrocardiográfico y tratamiento agudo de los episodios de fibrilación y flutter auricular.

Both atrial flutter and fibrillation are common arrhythmias in the clinical setting. Although we have been aware of them for decades, little has been known until recently about their triggering or maintenance mechanisms. The diagnosis of these arrhythmias lies largely in the electrocardiogram, which shows characteristic features of atrial electrical activity, leading to a correct diagnosis. Usually, some maneuvers such as adenosine infusion, carotidus sinus massage, etc., are required, in order to unmask the atrial activity, that are often obscured by the QRS complex or T wave. Several therapeutic options can be attempted for the acute termination of both atrial flutter and fibrillation episodes. The choice of one or another depends on some extent, on the clinical status of the patient during the arrhythmia, the presence of structural heart disease and the preceding arrhythmic history. Antiarrhythmic drugs are quite efficacious in the acute conversion of atrial fibrillation, but such an effect is not expected in atrial flutter. Drugs that depress AV nodal conduction can be used in both instances, as a therapeutic end-point or as a previous measure to the arrhythmia conversion. Direct current cardioversion is a good and efficacious option for both arrhythmias, however sedation is mandatory which, may be a contraindication in some patients. Rapid atrial pacing is an elegant and reliable method for the acute termination of atrial flutter of the common type, although a transvenous catheter insertion is needed.

[Radiofrequency ablation in permanent ectopic left atrial tachycardia]. / Radiofrequenzablation bei permanenter ektoper linksatrialer Tachykardie.

HISTORY AND FINDINGS: A 35-year-old symptom-free woman was known since childhood to have an increased resting heart rate (130-150/min). In the ECG there was a negative P in leads I and aVL, with a shortened P-Q interval of 90 ms. Previous treatment with beta-receptor blockers and calcium antagonists had failed. Clinical examination and echocardiography, as well as levels of thyroid hormone were unremarkable. During electrophysiological studies the earliest atrial activity was localised by endocardial leads in the region of the distal coronary sinus and the arrhythmia could not be terminated by atrial over-stimulation. TREATMENT AND COURSE: After transseptal puncture the ablation catheter was introduced into the left atrium and, the exact site of the origin of the atrial tachycardia having been established, radiofrequency ablation of this point was successfully performed. Subsequently the patient was always found to be in stable sinus rhythm at around 80/min. CONCLUSION: To prevent tachycardia-induced cardiomyopathy, radiofrequency ablation can be indicated even in symptom-free patients with atrial tachycardia.

Antispasmodic activity of benzylisoquinoline alkaloids analogous to papaverine.

In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.