Hemodynamic effects of Vernakalant in cardio-surgical ICU-patients treated for recent-onset postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF) is one of the most frequent complications after cardiothoracic surgery and a predictor for postoperative mortality and prolonged ICU-stay. Current guidelines suggest the multi-channel inhibitor Vernakalant as a treatment option for rhythm control. However, rare cases of severe hypotension and cardiogenic shock following drug administration have been reported. To elucidate the impact of Vernakalant on hemodynamics, we included ten ICU patients developing POAF after elective cardiac surgery, all of them awake and breathing spontaneously, in this prospective trial. Patients received the recommended dosage of Vernakalant and were clinically observed and monitored (heart rate, invasive blood pressure, pulse oximetry, central venous pressure) in 1-minute-intervals for 20 minutes before- and 120 minutes after the first dose of Vernakalant. The median time from the end of surgery until occurrence of POAF amounted up to 52.8 [45.9-77.4] hours, it took 3.5 [1.2-10.1] hours from occurrence of POAF until the first application of Vernakalant. All patients received catecholamine support with epinephrine that was held steady and not dynamic throughout the observational phase. We noted stable hemodynamic conditions, with a trend towards a reduction in heart rate throughout the 120 minutes after drug administration. In 7 patients (70%), conversion to sustained sinus rhythm (SR) occurred within 8.0 minutes [6.0-9.0]. No serious adverse events (SAEs) were noted during the observation period. In this prospective trial in ICU-patients showing POAF after cardiac surgery, intravenous Vernakalant did not induce clinically relevant negative effects on patients' hemodynamics but resulted in conversion to sustained SR after a median of 8.0 minutes in 7 out of ten patients.

Significant differences in access to tests and treatments for multiple myeloma between public and private systems in Latin America. Results of a Latin American survey. GELAMM (Grupo de Estudio Latino Americano de Mieloma Múltiple).

The incidence of multiple myeloma (MM) has increased in the last 20 years, particularly in middle and low-middle income countries. Access to diagnostic and prognostic tests and the availability of effective care is highly variable globally. Latin America represents 10% of the world population, distributed in countries of varied size, population, and socio-economic development. In the last decade, great improvements have been made in the diagnosis and treatment of MM. Applying these advances in real life is a challenge in our region. Local data regarding MM standards of care and outcomes are limited. A survey was carried out among hematologists from 15 Latin American countries to describe access to MM diagnostic and prognostic tests and the availability of effective care options. This study provides real-world data for MM in our region, highlighting striking differences between public and private access to essential analyses and therapeutic options.

[Rheumatoid arthritis and multiple myeloma as comorbidity. Is tocilizumab a therapy option?]. / Rheumatoide Arthritis und multiples Myelom als Komorbidität. Ist Tocilizumab eine Therapieoption?

Multiple myeloma (MM) is a disease of the elderly with an incidence of 4/100,000 per year and can occur as a comorbidity especially in elderly patients with rheumatoid arthritis (RA). For MM and also for RA interleukin-6 (IL-6) is a pathogenetically important cytokine in both disease events. This article presents the case of a female patient who achieved sustained remission of RA and stabilization of MM with quantitative reduction of paraprotein by treatment with tocilizumab. The question whether tocilizumab represents a meaningful treatment approach for treatment of RA when MM is also present will be discussed.

Cardioplegia and ventricular late potentials in cardiac surgical patients.

BACKGROUND AND OBJECTIVE: Ventricular late potentials (LP) recording with signal-averaged electrocar- diogram allow identifying patients at risk of sudden death and ventricular tachycardia. Cardiac surgery with cardiopulmonary bypass (CPB) could predispose to the development of myocardial ischemia related to imperfect cardioplegia. To the best of our knowledge, no study investigated the protection of cardioplegia and CPB regarding the occurrence of LP in patients without previous myocardial infarction and undergoing cardiac surgery. METHODS: In 61 elective patients scheduled for cardiac surgery involving CPB, signal-averaged electrocar- diogram was performed the day before and 24-48 h after the surgery. The electrodes were positioned according to Frank's orthogonal derivations. Twenty five patients were excluded because of poor quality signals, leaving 36 patients (age, 64 ± 14) available for the analyses. An abnormal signal-averaged electrocardiogram was considered when ≥2 of the recorded indexes were present. McNemar's tests were performed on the dichotomized values to investigate differences in pre-post scores. RESULTS: The mean CPB duration was of 110 ± 57 min. Patients scheduled for cardiac surgery do not exhibited LP after CPB (no significant difference in pre-post CPB scores, P = NS). The probability of a patient with a negative score transitioning to a positive score was 0.23 (P = NS). CONCLUSIONS: The present study in cardiac surgical patients suggests that cardioplegia associated to CPB has no significant impact on the occurrence of LP, irrespective of surgery performed.

[Viral arthritides]. / Virale Arthritiden.

Viruses are common etiologic agents of acute polyarthritis worldwide. Rheumatic symptoms are often accompanied by other viral symptoms such as fever, rash, myalgia or nausea, but isolated arthritis may occur resembling or imitating early rheumatoid arthritis. In Europe and North America, the most common arthritogenic viruses include parvovirus B19, rubella, hepatitis B and C, whereas mosquito-borne alpha-viruses are endemic in Africa, Australia, the western Pacific and South America. The latter have attracted the interest of European rheumatologists due to the increasing number of tourists travelling to these regions. Viruses may cause arthritis via various mechanisms, including direct synovial infection leading to cell lysis, immune complex formation or pro-inflammatory cytokine induction. Indirect viral pathogenic effects may induce autoimmune reactions via bystander activation or epitope spreading.

Transthoracic echocardiography after heart surgery: could pleural view be of some help?

The pericardial effusion localized on the upper portion of the right atrium is a classical complication of the post-operative heart surgery setting. This issue is most likely not visualized by transthoracic echocardiography and needs the transoesophageal approach. The present case reports a situation where an associated bilateral pleural effusion permitted a new view of the heart which has been helpful to confirm the diagnosis of tamponade and to re-transfer the patient to the operative room.

Neonatal procedural pain exposure and pain management in ventilated preterm infants during the first 14 days of life.

OBJECTIVES: Ventilated preterm infants are at high risk for procedural pain exposure. In Switzerland there is a lack of knowledge about the pain management in this highly vulnerable patient population. The aims of this study were to describe the type and frequency of procedures and to determine the amount of analgesia given to this patient group in two Swiss neonatal intensive care units. METHOD: A retrospective cohort study was performed examining procedural exposure and pain management of a convenience sample of 120 ventilated preterm infants (mean age = 29.7 weeks of gestation) during the first 14 days of life after delivery and born between May 1st 2004 and March 31st 2006. RESULTS: The total number of procedures all the infants underwent was 38,626 indicating a mean of 22.9 general procedures performed per child and day. Overall, 75.6% of these procedures are considered to be painful. The most frequently performed procedure is manipulation on the CPAP prongs. Pain measurements were performed four to seven times per day. In all, 99.2% of the infants received either non-pharmacological and/or pharmacological agents and 70.8% received orally administered glucose as pre-emptive analgesia. Morphine was the most commonly used pharmacological agent. DISCUSSION: The number of procedures ventilated preterm infants are exposed to is disconcerting. Iatrogenic pain is a serious problem, particularly in preterm infants of low gestational age. The fact that nurses assessed pain on average four to seven times daily per infant indicates a commitment to exploring a painful state in a highly vulnerable patient population. In general, pharmacological pain management and the administration of oral glucose as a non-pharmacological pain relieving intervention appear to be adequate, but there may be deficiencies, particularly for extremely low birth weight infants born <28 weeks of gestation.

Preoperative pulmonary hemodynamics determines changes in airway and tissue mechanics following surgical repair of congenital heart diseases.

To characterize the effect of changes in pulmonary hemodynamics on airway and tissue mechanics, forced oscillatory input impedance of the respiratory system (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing surgical repair of congenital heart disease (CHD) immediately before sternotomy and after chest closure during short apneic intervals. Children with lesions associated with high pulmonary blood flow and/or pressure (septal defects; HP group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot; LP group, n = 12) were included in the study. Airway resistance (Raw), and coefficients of respiratory tissue damping (G) and elastance (H), were estimated from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/- 9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/- 17%, no significance) after surgery. No significant change was observed in G in either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01) groups. These results suggest that the preoperative pulmonary hemodynamic condition determines changes in airway mechanics: surgical repair of CHD leads to an improvement in airway function only in children with congested lungs. The adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass may be responsible for the increased stiffness of the respiratory system observed in both groups of children.

Effects of volatile anaesthetic agents on enhanced airway tone in sensitized guinea pigs.

BACKGROUND: Although volatile anaesthetics afford protection against bronchospasm, their potential to reverse a sustained constriction of hyperreactive airways has not been characterized. Accordingly, we investigated the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung constriction induced by prolonged stimulation of the muscarinic receptors in guinea pigs sensitized to ovalbumin. METHODS: Pulmonary input impedance (ZL) was measured using forced oscillations in five groups of ovalbumin-sensitized, mechanically ventilated guinea pigs. ZL was measured under baseline conditions, during steady-state bronchoconstriction induced by an i.v. infusion of methacholine (MCh), and after administration of one of the volatile agents at 1 MAC after the induction of a steady-state bronchoconstriction. Airway resistance (Raw), and parenchymal tissue resistive and elastic coefficients were extracted from ZL by model fitting. RESULTS: All four volatile agents exhibited an initial relaxation of the MCh-induced airway constriction followed by gradual increases in Raw. The bronchodilatory effect of isoflurane was the most potent (-28.9 (SE 5.5)% at 2 min, P<0.05) and lasted longest (7 min); sevoflurane and halothane had shorter and more moderate effects (-21.1 (3.9)%, P<0.05, and -6.1 (1.7)%, P<0.05, respectively, at 1 min). Desflurane caused highly variable changes in Raw, with a tendency to enhance airway tone. CONCLUSIONS: Volatile agents can reverse sustained MCh-induced airway constriction only transiently in sensitized guinea pigs. Isoflurane proved most beneficial in temporally improving lung function in the presence of a severe constriction of allergic inflamed airways. Desflurane displayed potential to induce further airway constriction.

Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor.

The glioma amplified sequence 41 (GAS41) was previously isolated by microdissection mediated cDNA capture from the glioblastoma multiforme cell line TX3868 and shown to be frequently amplified in human gliomas. We determined the complete cDNA sequence of the GAS41 gene, demonstrated that the GAS41 protein is evolutionarily conserved, specifically at the N-terminus, and identified the yeast transcription factor tf2f domain within the GAS41 sequence. A human multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the highest expression in human brain. After generating polyclonal antibodies we found GAS41 protein expression in the nucleus of the TX3868 cell line by Western blot analysis and immunofluorescence microscopy. The nuclear localization was confirmed for several human tumors including gliomas of different grades of malignancy. In neuroblastoma however, GAS41 was found in the nucleoli but not in the nucleoplasm. Yeast two-hybrid screening of the TX3868 cell line identified the nuclear mitotic apparatus protein (NuMA), the KIAA1009 protein, and prefoldin subunit 1 (PFDN1) as potential interacting partners of GAS41. We generated a polyclonal antibody against the KIAA1009 protein and we demonstrated that the KIAA1009 protein is a nuclear protein, which appears to be co-localized with the GAS41 protein and NuMA.

Structure and expression of the human p68 RNA helicase gene.

Nuclear DEAD box protein p68 is immunologically related to SV40 large tumour antigen and both proteins possess RNA helicase activity. In this report, we describe the structural organisation of the human p68 gene and aspects of the regulation of its expression. Northern blot and primer extension analyses indicate that, although its level is variable, the p68 RNA helicase appears to be expressed from a single transcription start site in all tissues tested. Sequence analysis revealed that the p68 promoter harbours a 'TATA', a 'CAAT' and an initiator element and contains high affinity binding sites for Sp1, AP-2, CRE and Myc. This and functional promoter analyses in transient expression assays suggest that transcriptional regulation of the p68 gene is complex. Furthermore, there are indications that p68 expression is also regulated post-transcriptionally. Steady-state pools of poly(A)(+)RNA from human cells contain completely spliced p68 mRNA and alternatively spliced forms that contain introns 8-11 or 8-12 (from a total of 12 introns) and are not translated. Analysis of a conditionally p68-overproducing HeLa cell line points to negative autoregulation at the level of splicing, which is confirmed by a recently reported association of p68 with spliceosomes in human cells.