Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Eight new Halophytophthora species from marine and brackish-water ecosystems in Portugal and an updated phylogeny for the genus.

During an oomycete survey in December 2015, 10 previously unknown Halophytophthora taxa were isolated from marine and brackish water of tidal ponds and channels in saltmarshes, lagoon ecosystems and river estuaries at seven sites along the Algarve coast in the South of Portugal. Phylogenetic analyses of LSU and ITS datasets, comprising all described Halophytophthora species, the 10 new Halophytophthora taxa and all relevant and distinctive sequences available from GenBank, provided an updated phylogeny of the genus Halophytophthora s.str. showing for the first time a structure of 10 clades designated as Clades 1-10. Nine of the 10 new Halophytophthora taxa resided in Clade 6 together with H. polymorphica and H. vesicula. Based on differences in morphology and temperature-growth relations and a multigene (LSU, ITS, Btub, hsp90, rpl10, tigA, cox1, nadh1, rps10) phylo-geny, eight new Halophytophthora taxa from Portugal are described here as H. brevisporangia, H. cele-ris, H. frigida, H. lateralis, H. lusitanica, H. macrosporangia, H. sinuata and H. thermoambigua. Three species, H. frigida, H. macrosporangia and H. sinuata, have a homothallic breeding system while the remaining five species are sterile. Pathogenicity and litter decomposition tests are underway to clarify their pathological and ecological role in the marine and brackish-water ecosystems. More oomycete surveys in yet undersurveyed regions of the world and population genetic or phylogenomic analyses of global populations are needed to clarify the origin of the new Halophytophthora species. Citation: Maia C, Horta Jung M, Carella G, et al. 2022. Eight new Halophytophthora species from marine and brackish-water ecosystems in Portugal and an updated phylogeny for the genus. Persoonia 48: 54 - 90. https://doi.org/10.3767/persoonia.2022.48.02..

Extensive morphological and behavioural diversity among fourteen new and seven described species in Phytophthora Clade 10 and its evolutionary implications.

During extensive surveys of global Phytophthora diversity 14 new species detected in natural ecosystems in Chile, Indonesia, USA (Louisiana), Sweden, Ukraine and Vietnam were assigned to Phytophthora major Clade 10 based on a multigene phylogeny of nine nuclear and three mitochondrial gene regions. Clade 10 now comprises three subclades. Subclades 10a and 10b contain species with nonpapillate sporangia, a range of breeding systems and a mainly soil- and waterborne lifestyle. These include the previously described P. afrocarpa, P. gallica and P. intercalaris and eight of the new species: P. ludoviciana, P. procera, P. pseudogallica, P. scandinavica, P. subarctica, P. tenuimura, P. tonkinensis and P. ukrainensis. In contrast, all species in Subclade 10c have papillate sporangia and are self-fertile (or homothallic) with an aerial lifestyle including the known P. boehmeriae, P. gondwanensis, P. kernoviae and P. morindae and the new species P. celebensis, P. chilensis, P. javanensis, P. multiglobulosa, P. pseudochilensis and P. pseudokernoviae. All new Phytophthora species differed from each other and from related species by their unique combinations of morphological characters, breeding systems, cardinal temperatures and growth rates. The biogeography and evolutionary history of Clade 10 are discussed. We propose that the three subclades originated via the early divergence of pre-Gondwanan ancestors > 175 Mya into water- and soilborne and aerially dispersed lineages and subsequently underwent multiple allopatric and sympatric radiations during their global spread. Citation: Jung T, Milenkovic I, Corcobado T, et al. 2022. Extensive morphological and behavioural diversity among fourteen new and seven described species in Phytophthora Clade 10 and its evolutionary implications. Persoonia 49: 1-57. https://doi.org/10.3767/persoonia.2022.49.01.

Single-Phonon Addition and Subtraction to a Mechanical Thermal State.

Adding or subtracting a single quantum of excitation to a thermal state of a bosonic system has the counter-intuitive effect of approximately doubling its mean occupation. We perform the first experimental demonstration of this effect outside optics by implementing single-phonon addition and subtraction to a thermal state of a mechanical oscillator via Brillouin optomechanics in an optical whispering-gallery microresonator. Using a detection scheme that combines single-photon counting and optical heterodyne detection, we observe this doubling of the mechanical thermal fluctuations to a high precision. The capabilities of this joint click-dyne detection scheme adds a significant new dimension for optomechanical quantum science and applications.

Non-Gaussian Mechanical Motion via Single and Multiphonon Subtraction from a Thermal State.

Quantum optical measurement techniques offer a rich avenue for quantum control of mechanical oscillators via cavity optomechanics. In particular, a powerful yet little explored combination utilizes optical measurements to perform heralded non-Gaussian mechanical state preparation followed by tomography to determine the mechanical phase-space distribution. Here, we experimentally perform heralded single-phonon and multiphonon subtraction via photon counting to a laser-cooled mechanical thermal state with a Brillouin optomechanical system at room temperature and use optical heterodyne detection to measure the s-parametrized Wigner distribution of the non-Gaussian mechanical states generated. The techniques developed here advance the state of the art for optics-based tomography of mechanical states and will be useful for a broad range of applied and fundamental studies that utilize mechanical quantum-state engineering and tomography.

Rate Control by Transoesophageal Atrial Overdrive Pacing for Refractory Supraventricular Tachycardia with Severe Ventricular Dysfunction: A Bridge to Recovery.

Tachyarrhythmia-induced cardiomyopathy (TIC) is a rare, yet life-threatening phenomenon in children. TIC has been defined as myocardial dysfunction that is entirely or partially reversible after control of the responsible tachyarrhythmia and is typically caused by an incessant supraventricular tachycardia. In cases of unsuccessful termination of the tachycardia, cardiogenic shock may occur. Several authors favour the use of mechanical circulatory support in such cases. Particularly with regard to these partly severe cases, the authors would like to present the option of transoesophageal overdrive pacing (TOP) as a tool for initial heart rate control and hemodynamic stabilization of patients with TIC refractory to conventional strategies of tachycardia termination. Chart review for patients receiving TOP during the last 5 years in two centres was performed. A case series of successful TOP including technique and outcomes is depicted. Rate control through TOP is a safe and effective option to restore acceptable hemodynamics in infants with refractory supraventricular tachycardia and severe impairment of ventricular function. It presents the possibility of immediate heart rate control and offers time for myocardial recovery and safe implementation of antiarrhythmic drug therapy.

Squeezed light from a diamond-turned monolithic cavity.

For some crystalline materials, a regime can be found where continuous ductile cutting is feasible. Using precision diamond turning, such materials can be cut into complex optical components with high surface quality and form accuracy. In this work we use diamond-turning to machine a monolithic, square-shaped, doubly-resonant LiNbO3 cavity with two flat and two convex facets. When additional mild polishing is implemented, the Q-factor of the resonator is found to be limited only by the material absorption loss. We show how our monolithic square resonator may be operated as an optical parametric oscillator that is evanescently coupled to free-space beams via birefringent prisms. The prism arrangement allows for independent and large tuning of the fundamental and second harmonic coupling rates. We measure 2.6 ± 0.5 dB of vacuum squeezing at 1064 nm using our system. Potential improvements to obtain higher degrees of squeezing are discussed.

[Cardiac Resynchronization Therapy in the Treatment of Heart Failure in Children].

Cardiac resynchronizing therapy (CRT) is currently a leading approach to the treatment of heart failure in adults. However, data regarding application of CRT in children remain limited and indications for CRT are unclear. There is evidence that the best treatment outcomes result from the administration of CRT to the group of children whose heart failure is caused by dyssynchrony mediated by traditional stimulation of the right ventricle in patient with complete atrioventricular block. On the contrary, the presence of dilated cardiomyopathy and functional class III-IV heart failure are the predictors of ineffective CRT. Implantation of CRT devices in children has many peculiarities and challenges associated with anatomic and physiological characteristics of childhood age. Taking into consideration the expected length of treatment, one should admit that epicardial biventricular stimulation should be preferred. In the present paper the authors discuss pathophysiology of the electromechanical dyssynchrony, analyze their own experience with CRT, and suggest indications for this kind of treatment.

Outcome of resynchronization therapy on superficial and endocardial electrophysiological findings.

Cardiac resynchronization therapy (CRT) has proven efficacious in the treatment of patients with heart failure and dyssynchronous activation. Currently, we select suitable CRT candidates based on the QRS complex duration (QRSd) and morphology with left bundle branch block being the optimal substrate for resynchronization. To improve CRT response rates, recommendations emphasize attention to electrical parameters both before implant and after it. Therefore, we decided to study activation times before and after CRT on the body surface potential maps (BSPM) and to compare thus obtained results with data from electroanatomical mapping using the CARTO system. Total of 21 CRT recipients with symptomatic heart failure (NYHA II-IV), sinus rhythm, and QRSd >/=150 ms and 7 healthy controls were studied. The maximum QRSd and the longest and shortest activation times (ATmax and ATmin) were set in the BSPM maps and their locations on the chest were compared with CARTO derived time interval and site of the latest (LATmax) and earliest (LATmin) ventricular activation. In CRT patients, all these parameters were measured during both spontaneous rhythm and biventricular pacing (BVP) and compared with the findings during the spontaneous sinus rhythm in the healthy controls. QRSd was 169.7+/-12.1 ms during spontaneous rhythm in the CRT group and 104.3+/-10.2 ms after CRT (p<0.01). In the control group the QRSd was significantly shorter: 95.1+/-5.6 ms (p<0.01). There was a good correlation between LATmin(CARTO) and ATmin(BSPM). Both LATmin and ATmin were shorter in the control group (LATmin(CARTO) 24.8+/-7.1 ms and ATmin(BSPM) 29.6+/-11.3 ms, NS) than in CRT group (LATmin(CARTO) was 48.1+/-6.8 ms and ATmin(BSPM) 51.6+/-10.1 ms, NS). BVP produced shortening compared to the spontaneous rhythm of CRT recipients (LATmin(CARTO) 31.6+/-5.3 ms and ATmin(BSPM) 35.2+/-12.6 ms; p<0.01 spontaneous rhythm versus BVP). ATmax exhibited greater differences between both methods with higher values in BSPM: in the control group LATmax(CARTO) was 72.0+/-4.1 ms and ATmax (BSPM) 92.5+/-9.4 ms (p<0.01), in the CRT candidates LATmax(CARTO) reached only 106.1+/-6.8 ms whereas ATmax(BSPM) 146.0+/-12.1 ms (p<0.05), and BVP paced rhythm in CRT group produced improvement with LATmax(CARTO) 92.2+/-7.1 ms and ATmax(BSPM) 130.9+/-11.0 ms (p<0.01 before and during BVP). With regard to the propagation of ATmin and ATmax on the body surface, earliest activation projected most often frontally in all 3 groups, whereas projection of ATmax on the body surface was more variable. Our results suggest that compared to invasive electroanatomical mapping BSPM reflects well time of the earliest activation, however provides longer time-intervals for sites of late activation. Projection of both early and late activated regions of the heart on the body surface is more variable than expected, very likely due to changed LV geometry and interposed tissues between the heart and superficial ECG electrode.

Observation of a comb of optical squeezing over many gigahertz of bandwidth.

We experimentally demonstrate the generation of optical squeezing at multiple longitudinal modes and transverse Hermite-Gauss modes of an optical parametric amplifier. We present measurements of approximately 3 dB squeezing at baseband, 1.7 GHz, 3.4 GHz and 5.1 GHz which correspond to the first, second and third resonances of the amplifier. We show that both the magnitude and the bandwidth of the squeezing at the higher longitudinal modes is greater than can be observed at baseband. The squeezing observed is the highest frequency squeezing reported to date.

Electrocardiographic outcome of resynchronization therapy.

Cardiac resynchronization therapy (CRT) has proven efficacious in reducing or even eliminating cardiac dyssynchrony and thus improving heart failure symptoms. However, quantification of mechanical dyssynchrony is still difficult and identification of CRT candidates is currently based just on the morphology and width of the QRS complex. As standard 12-lead ECG brings only limited information about the pattern of ventricular activation, we aimed to study changes produced by different pacing modes on the body surface potential maps (BSPM). Total of 12 CRT recipients with symptomatic heart failure (NYHA II-IV), sinus rhythm and QRS width >/=120 ms and 12 healthy controls were studied. Mapping system Biosemi (123 unipolar electrodes) was used for BSPM acquisition. Maximum QRS duration, longest and shortest activation times (ATmax and ATmin) and dispersion of QT interval (QTd) were measured and/or calculated during spontaneous rhythm, single-site right- and left-ventricular pacing and biventricular pacing with ECHO-optimized AV delay. Moreover we studied the impact of CRT on the locations of the early and late activated regions of the heart. The average values during the spontaneous rhythm in the group of patients with dyssynchrony (QRS 140.5+/-10.6 ms, ATmax 128.1+/-10.1 ms, ATmin 31.8+/-6.7 ms and QTd 104.3+/-24.7 ms) significantly differed from those measured in the control group (QRS 93.0+/-10.0 ms, ATmax 79.1+/-3.2 ms, ATmin 24.4+/-1.6 ms and QTd 43.6+/-10.7 ms). Right ventricular pacing (RVP) improved significantly only ATmax [111.2+/-10.6 ms (p<0.05)] but no other measured parameters. Left ventricular pacing (LVP) succeeded in improvement of all parameters [QRS 105.1+/-8.0 ms (p<0.01), ATmax 103.7+/-7.1 ms (p<0.01), ATmin 20.2+/-3.7 ms (p<0.01) and QTd 52.0+/-9.4 ms (p<0.01)]. Biventricular pacing (BVP) showed also a beneficial effect in all parameters [QRS 121.3+/-8.9 ms (p<0.05), ATmax 114.3+/-8.2 ms (p<0.05), ATmin 22.0+/-4.1 ms (p<0.01) and QTd 49.8+/-10.0 ms (p<0.01)]. Our results proved beneficial outcome of LVP and BVP in evaluated parameters (what seems to be important particularly in the case of activation times) and revealed a complete return of activation times to normal distribution when using these CRT modalities.

Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot.

BACKGROUND: Chronic pulmonary regurgitation after repair of tetralogy of Fallot (TOF) may lead to right ventricular dilatation, which may be accompanied by ventricular tachycardia and sudden death. We aimed to examine the effects of pulmonary valve replacement (PVR) on (1) certain electrocardiographic markers predictive of monomorphic ventricular arrhythmia and sudden death and (2) sustained atrial flutter/fibrillation and monomorphic ventricular tachycardia. METHODS AND RESULTS: We studied 70 patients who underwent PVR for pulmonary regurgitation and/or right ventricular outflow tract obstruction late after repair of TOF. Maximum QRS duration and QT dispersion were measured from standard ECGs before PVR and at the latest follow-up. Arrhythmia was defined as sustained atrial flutter/fibrillation or sustained monomorphic ventricular tachycardia. Concomitant intraoperative electrophysiological mapping and/or cryoablation were performed in 9 patients (60%) with preexisting ventricular tachycardia and 6 patients (50%) with preexisting atrial flutter. QRS duration remained unchanged in the study group (P=0.46), but it was significantly prolonged (P<0.001) in a comparable group of patients with repaired TOF who did not undergo PVR. At a mean follow-up of 4.7 years, the incidence of ventricular tachycardia diminished from 22% to 9% (P<0.001), and atrial flutter/fibrillation decreased from 17% to 12% (P=0.32). Intraoperative ablation prevented recurrence of preexisting tachyarrhythmia (0 of 15 patients). CONCLUSIONS: PVR in patients with previous TOF repair and chronic pulmonary regurgitation leads to stabilization of QRS duration and, in conjunction with intraoperative cryoablation, to a decrease in the incidence of preexisting atrial and ventricular tachyarrhythmia. When applicable, this combined approach should be used in patients late after repair of TOF.

Efficacy and safety of propafenone in congenital junctional ectopic tachycardia.

OBJECTIVES: Class IC antiarrhythmic drugs have recently been shown to be effective in some patients with atrial ectopic tachycardia. We therefore studied the efficacy of these drugs in patients with congenital junctional ectopic tachycardia. BACKGROUND: Follow-up data on patients with junctional ectopic tachycardia suggest that this potentially lethal arrhythmia may cease spontaneously in a significant proportion of affected children. Therefore, temporary antiarrhythmic treatment appears to be the therapy of choice. METHODS: The efficacy of propafenone was prospectively assessed in four infants with junctional ectopic tachycardia (ventricular rate 180, 185, 210 and 320 beats/min, respectively). The diagnosis of junctional ectopic tachycardia was established before the age of 2 months in all four infants. Propafenone was given orally in a mean dose of 350 (300 to 500) mg/m2 body surface area per day. Success of therapy was determined by serial electrocardiograms (ECGs) and Holter ambulatory ECG monitoring. RESULTS: In two patients, junctional ectopic tachycardia was completely suppressed. In the remaining two patients, the tachycardia rate decreased to less than 150 beats/min. Serum propafenone levels did not correlate with efficacy of treatment. The mean duration of therapy was 18 months (range 3 to 36). No chemical or clinical side effects were noted. CONCLUSIONS: Because of its effectiveness, safety and lack of side effects, propafenone appears to be a valuable drug in the treatment of junctional ectopic tachycardia in newborns and infants.

Reduction of incorrect antibiotic dosing through a structured educational order form.

Antibiotics are often used inappropriately in hospitals. We created a structured antibiotic order form designed to guide physicians toward correct therapeutic decisions without restricting their clinical options. Educational messages and graphic reminders were incorporated into a new form required to order parenteral antibiotics at a teaching hospital. Pharmacokinetic considerations were emphasized. The forms were supplemented with brief literature reviews and appropriate references. Before introduction of the form, pharmacokinetically incorrect orders for clindamycin, cefazolin sodium, and metronidazole hydrochloride accounted for 90%, 60%, and 75% of patient-days of therapy for these drugs, respectively. Immediately after implementation of the form, nonrecommended dosing schedules dropped to under 6% of patient-days for all three antibiotics. Savings from these drugs alone accounted for over $76,000 annually. We conclude that in a period of increasing constraints on hospital budgets and proliferating restrictions on physicians' clinical choices, educational intervention at the time orders are written can provide a cost-effective and noncoercive means of improving some forms of acute-care clinical decision making.

Purification of murine Kupffer cells by centrifugal elutriation.

Procedures to reproducibly obtain pure preparations of murine Kupffer cells are described. Pure Kupffer cell preparations obtained following collagenase digestion, metrizamide separation and centrifugal elutriation remained viable and maintained their phagocytic functions for at least 4-5 days in vitro. Furthermore, we determined the feasibility of extracting RNA from Kupffer cells obtained immediately following elutriation and after 2 and 4 days of culture in vitro. These RNA extracts were used to determine the level of cytokine gene expression in Kupffer cells.

Safety of oral propafenone in the treatment of arrhythmias in infants and children (European retrospective multicenter study). Working Group on Pediatric Arrhythmias and Electrophysiology of the Association of European Pediatric Cardiologists.

This study was designed to assess adverse effects of oral propafenone in a large number of pediatric patients. Retrospective data from 27 European centers covering 772 patients treated with oral propafenone were analyzed. The following arrhythmias were treated: reentrant supraventricular tachycardia in 388 patients, atrial ectopic tachycardia in 66, junctional ectopic tachycardia in 39, atrial flutter in 21, ventricular premature complexes in 140, ventricular tachycardia in 78, and other arrhythmias in 39 patients. Two hundred forty-nine patients (32.3%) had structural heart disease. Significant electrophysiologic side effects and proarrhythmia were found in 15 of 772 patients (1.9%): sinus node dysfunction in 4, complete atrioventricular block in 2, aggravation of supraventricular tachycardia in 2, acceleration of ventricular rate during atrial flutter in 1, ventricular proarrhythmia in 5, and unexplained syncope in 1 patient. Cardiac arrest or sudden death occurred in 5 of 772 patients (0.6%): 2 patients had supraventricular tachycardia due to the Wolff-Parkinson-White syndrome and a normal heart; the remaining 3 patients had structural heart disease. Overall, adverse cardiac events were more common in the presence (12 of 249 patients, 4.8%) than in the absence (8 of 523 patients, 1.5%) of structural heart disease (p <0.01). There was no difference between patients treated for supraventricular and ventricular arrhythmias. Thus, propafenone is a relatively safe drug for the treatment of several pediatric tachyarrhythmias. Proarrhythmic effects seem to be less frequent than those reported for encainide or flecainide and occur predominantly in patients with structural heart disease.

Role of late potentials in identifying patients at risk for ventricular tachycardia after surgical correction of congenital heart disease.

This study evaluates the role of late potentials in identifying patients with sustained ventricular tachycardia (VT) after surgery for congenital heart defects using right ventriculotomy. Nine patients with early (1 to 12 months) or late VT (spontaneous in 7 [induced during electrophysiologic study in 6 of the 7] and induced in 2) and 104 patients without VT were studied. All patients had complete right bundle branch block. Late potentials were quantified by 3 time-domain parameters of the signal-averaged electrocardiogram: total filtered QRS duration, root-mean-square voltage in the last 40 ms, and low-amplitude signal duration of the terminal filtered QRS complex. Root-mean-square voltage filtered at 80 to 250 Hz was lower in patients with than without VT (9 +/- 6 vs 16 +/- 8 microV, p < 0.01). By multivariate analysis, more complex surgery (i.e., insertion of extracardiac conduits, Kawashima operation, etc.), lower root-mean-square voltage, and higher Lown grade (2 to 5) of ventricular arrhythmias on routine postoperative Holter recordings were the only independent predictors of VT (p < 0.001, < 0.05, and < 0.05, respectively). A combination of more complex surgery, root-mean-square voltage < 14 microV, and Lown grade 2 to 5 ventricular arrhythmias was highly predictive of VT (positive predictive value 75%). Conversely, patients without complex surgery and with root-mean-square voltage of > 13 microV were not likely to develop VT (negative predictive value 100%). Late potentials are an independent predictor of VT and may improve the identification of patients at low and high risk of VT after surgery for congenital heart defects using right ventriculotomy.

Usefulness of propafenone for supraventricular arrhythmias in infants and children.

The relation between propafenone dose, serum level, electrocardiographic parameters, antiarrhythmic drug efficacy and adverse effects was studied in 47 children with symptomatic supraventricular arrhythmias aged 1 day to 10.3 years (median 2.2 months) with a mean follow-up of 14.3 months. Propafenone trough serum levels were measured using gas chromatography. Oral propafenone (mean dose 353 mg/m2/day) was effective in 41 of the 47 patients (87.2%). Serum levels did not differ between patients responding and not responding to propafenone (0.45 +/- 0.40 vs 0.36 +/- 0.41 mg/liter). PR interval and QRS complex duration increased more significantly with propafenone dose increments (p < 0.001), than with propafenone serum levels (p < 0.05). At successful treatment PR interval and QRS complex were prolonged by a mean of 19.2 and 20.5% compared with pretreatment status. Five patients exhibited unexpected marked QRS complex prolongation (50 to 200%) despite low propafenone dosage (< 300 mg/m2/day) and level ranging from 0.05 to 1.33 mg/liter. Three patients (6.1%) were suspected of being "poor" metabolizers of propafenone. Mild chronic elevation of serum liver enzymes was observed in 5 patients treated with a larger dose (mean 448 mg/m2/day, p < 0.001). No proarrhythmia was noted on serial Holter monitors. One patient with Wolff-Parkinson-White syndrome and a normal heart had cardiac arrest after aspiration. Serial monitoring of PR interval and QRS complex duration was more useful for proper dosage adjustment than propafenone serum levels. Serum liver enzymes should be closely monitored when using higher propafenone doses. Malignant proarrhythmia could not be excluded in the 1 patient with cardiac arrest.

Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects.

The acute hemodynamic effect of atrioventricular (AV) and inter/intraventricular (IV) resynchronization accomplished by temporary pacing using multiple epicardial pacing wires was evaluated in 20 children (aged 3.4 months to 14.0 years) after surgery for congenital heart defects fulfilling the following criteria: (1) presence of AV and/or IV conduction delay, and (2) need for inotropic support. AV resynchronization (n = 13) was achieved by AV delay optimization during atrial synchronous right ventricular outflow tract pacing. IV resynchronization (n = 14) was accomplished by atrial synchronous pacing from the right ventricular lateral wall in 7 patients with right bundle branch block and normal AV conduction and by atrial synchronous multisite ventricular pacing in another 7 patients with previously performed AV resynchronization. Compared with baseline values, AV resynchronization resulted in an increase in arterial systolic, mean, and pulse pressures by 7.2 +/- 8.3% (p <0.01), 8.6 +/- 8.1% (p <0.005), and 6.9 +/- 13.5% (p = NS), respectively. IV resynchronization used either alone or added to previously performed AV resynchronization led to a pressure increase of 7.0 +/- 4.7%, 5.9 +/- 4.7%, and 9.4 +/- 7.8%, respectively (p <0.001 for all). The combined effect of AV and IV resynchronization resulted in a systolic, mean, and pulse pressure increase of 10.2 +/- 5.0% (range 4.0 to 19.1), 8.6 +/- 5.4% (range 0.8 to 14.8), and 15.2 +/- 8.5% (range 6.1 to 33.3), respectively (p <0.001 for all). The increase in systolic arterial pressure after IV resynchronization was positively correlated with the initial QRS duration (r = 0.62, p <0.05) and extent of QRS shortening (r = 0.66, p <0.05). In conclusion, resynchronization pacing led to a significant increase in arterial blood pressure and was a useful adjunct to the treatment of acute postoperative heart failure in patients with AV and/or IV conduction delay.

Nitrogen balance, 3-methylhistidine excretion, and plasma amino acid profile in infants after cardiac operations for congenital heart defects: the effect of early nutritional support.

OBJECTIVE: The objective of this study was to evaluate the effect of nutritional support on proteolysis and plasma amino acid profile in infants early after cardiac operations for congenital heart defects. METHODS: Thirty-seven patients, 2 to 12 months old, were randomized on postoperative day 1 for 24-hour isocaloric metabolic study. Group STANDARD (18 patients) received glucose as the maintenance fluid, and group PN (19 patients) received glucose and crystalloid amino acid solution at a dosage of 0.8 +/- 0.1 gm/kg per day. The nonprotein caloric intake in the two groups was 25 +/- 15 and 33 +/- 9 kcal/kg, respectively (p = not significant). RESULTS: The nitrogen balance was markedly less negative in group PN than in group STANDARD (-114 +/- 81 vs -244 +/- 86 mg/kg, respectively, p = 0.001). There was a highly significant inverse correlation between the nitrogen balance and urinary 3-methylhistidine excretion in both groups, but the muscle proteolysis was blunted more effectively in patients receiving amino acids. Concentrations of the plasmatic branched-chain amino acids, alanine, glycine, and proline, decreased significantly in group STANDARD but not in group PN on postoperative day 2. Glutamine and threonine levels declined significantly on postoperative day 2 in both groups. Low levels of arginine were observed in our patients before operation and in the early postoperative period. The amino acid concentrations normalized on postoperative day 7 in all patients. CONCLUSION: Significant proteolysis and hypoaminoacidemia were observed in infants early after cardiac operations. This hypercatabolic response was blunted by parenteral nutritional support.