Bidirectional transvenous/subcutaneous defibrillation of ventricular fibrillation in dogs: success rates, energy requirements, currents, voltages and impedance

Four hundred and thirteen defibrillations of alternating current-inducedventricular fibrillation were performed in 10 halothane-anaesthetizeddogs (body weight: 24.5–30.5 kg). Success rates, energydemands, currents, peak voltages and impedance were determined.A transvenous catheter electrode system (Medtronic 6880, rightventricular apex and superior vena cava, distance 100 or 150mm) and subcutaneous patch electrodes (Intec 67 L, 2nd/3rd and/or3rd/4th left intercostal space) were used for bidirectionaldefibrillation. Loading voltages ranged from 600 to 850 V. Withan electrode distance of 100 mm and a pulse duration of 2 msseparated by 1 ms, success rates were 100%, 40% and 0% for 850,650 and 600 V, respectively. With a 3-ms pulse duration, thecorresponding rates were 100%, 60% and 50%. With a 2-ms pulseduration, successful defibrillation was achieved with energieslower than 15 J in 27%, with energies between 15 and 20 J in77%, and 100% with energies higher than 20 J. Defibrillationcurrents were 4.4–9.3 A for pulse 1 (superior vena cava/ventricularapex) and 6.3–13.4 A for pulse 2 (patch/ventricular apex),respectively. Effective peak voltages ranged from 510 to 787V and from 514 to 777 V and averaged 89.6% of the loading voltages.Impedance values (peak voltage/current) were 75.5–117.7(pulse 1) and 51.7–94.9 Ohms (pulse 2). Fifty consecutivedefibrillations in one animal resulted in a decrease of impedance(114.6 to 84.9 Ohms, pulse 1; 75.4 to 53.0 Ohms, pulse 2). Defibrillationof ventricular fibrillation can be achieved with acceptablylow energies using a bidirectional transvenous/subcutaneoussystem, avoiding thoracotomy and general anaesthesia for implantationof the defibrillation system.     

胚胎种植前遗传学检测助孕妊娠结局的影响因素研究

背景 育龄期女性胚胎着床失败及流产的最常见原因是胚胎异常,但移植经胚胎种植前遗传学检测(PGT)筛选后的正常胚胎后,仍出现种植失败或流产的原因目前并没有形成统一的结论。目的 分析PGT助孕后种植失败及流产的影响因素。方法 回顾性分析2018年12月至2021年2月在安徽医科大学第一附属医院生殖中心行PGT助孕的329例患者的临床资料,根据患者是否临床妊娠分为临床妊娠组(n=218)和种植失败组(n=111),并将临床妊娠组患者根据妊娠结局分为活产亚组(n=175)和流产亚组(n=43)。比较临床妊娠组和种植失败组,活产亚组和流产亚组的一般情况、促排卵及体外胚胎发育情况。采用多因素Logistic回归分析探讨PGT患者种植失败及流产的影响因素。绘制受试者工作特征(ROC)曲线分析多因素Logistic回归分析筛选出的影响因素对PGT患者发生种植失败及流产的预测价值。结果 多因素Logistic回归分析显示,既往流产次数≥2次〔OR=4.032 0,95%CI(2.423 0,6.710 0)〕、高密度脂蛋白胆固醇(HDL-C)水平低〔OR=3.890 0,95%CI(1.455 0,10...     

Die Rolle coagulasenegativer Staphylokokken in Mischinfektionen: Assoziationstestungen als in-vitro-Modell

Zusammenfassung Die Zunahme von Infektionen durch hochresistente grampositive Kokken hat in den letzten Jahren vornehmlich auf Intensivstationen zu erheblichen therapeutischen Problemen geführt. Hierbei ist eine Gruppe von Erregern in den Vordergrund getreten, die früher als harmlose Saprophyten galten: coagulasenegative Staphylokokken (CNS). In der vorliegenden Arbeit werden zunächst Daten zur Incidenz in verschiedenen Versorgungsbereichen unserer Klinik und zur Coincidenz mit anderen Erregern auf unserer Intensivstation vorgestellt. Es konnte gezeigt werden, daßS. aureus zwar der zahlenmäßig häufigste grampositive Erreger war, aber CNS sowohl aus Wundabstrichen der Intensivstation als auch aus Blutkulturen deutlich häufiger isoliert werden konnte. Ein gleichzeitiger Nachweis von CNS mitS. aureus und den neun häufigsten Enterobacteriaceae konnte in durchschnittlich 6% erbracht werden. Durch mögliche Interaktionen zwischen unterschiedlichen Erregern kann eine Veränderung der in Einzeltestung beobachteten Resistenzen auftreten. Um dies nachzuweisen, wurden sechs Erregerpaare einzeln und in Assoziation gegen Amoxicillin und Amoxicillin/Clavulansäure getestet. Unter Assoziation wurde das gemeinsame Wachstum zweier Keime unter kontrollierten Bedingungen in Boullionverdünnungsreihen oder einem Laborautomaten zur Resistenztestung (Cobas Bact) verstanden. In allen Fällen zeigte sich, daß die-Lactamasen der CNS in Assoziation die MHK der anderen Erreger deutlich erhöhte, was durch den Zusatz von Clavulansäure verhindert werden konnte. Eine Einzeltestung gibt also bei Mischinfekten mit Beteiligung von-Lactamasebildnern nur einen eingeschränkten Eindruck von der tatsächlichen Resistenzsituation.

---

Role of coagulase negative staphylococci in mixed infections: associative testing as in vitro model

Summary Infections due to coagulase negative staphylococci (CNS) are of growing concern mainly in patients hospitalized in intensive care units (ICU). The ability of CNS to adhere and to grow on plastic devices and resistance to many antibiotics, including oxacillin, contributes to their pathogenicity. Using the computer assisted system of the Medical Microbiology Department, the incidences of different pathogens and the coincidence of CNS with other bacteria were evaluated in a surgical department.Staphylococcus aureus revealed to be the predominant pathogen; however, CNS showed an increasing incidence in wound specimens and blood cultures of patients on the ICU. Coincidence of CNS withS. aureus and the nine most frequent species of gram negative bacteria could be shown in 6%. To investigate the influence of-lactamases produced by CNS in mixed infections, association experiments were performed. Association means a controlled growth of two or even more bacteria in a susceptibility testing system, either a broth dilution method or an automated broth disk elution method (Cobas Bact). The association experiments showed a significant increase of amoxicillin MIC's of the pathogen associated with CNS. Addition of clavulanic acid restored activity of amoxicillin. It could be shown that in mixed infections CNS may contribute to the failure of antibiotic regimens by production of-lactamases.

     

Transdermal Dual-Controlled Delivery of Contraceptive Drugs: Formulation Development,in Vitro and in Vivo Evaluations,and Clinical Performance

Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17-estradiol (E₂), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E₂ from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia–Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45°C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm²). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects.     

Rapid diagnosis of parasitic diseases: current scenario and future needs

Background

Parasitic diseases are one of the world's most devastating and prevalent infections, causing millions of morbidities and mortalities annually. In the past, many of these infections have been linked predominantly to tropical or subtropical areas. Nowadays, however, climatic and vector ecology changes, a significant increase in international travel, armed conflicts, and migration of humans and animals have influenced the transmission of some parasitic diseases from ‘book pages’ to reality in developed countries. It has also been noted that many patients who have never travelled to endemic areas suffer from blood-borne infections caused by protozoa. In the light of existing knowledge, this new trend can be explained by the fact that in the process of migration a large number of asymptomatic carriers become a part of the blood bank donor and transplant donor populations. Accurate and rapid diagnosis represents the crucial weapon in the fight against parasitic infections.

Zika virus diagnosis: challenges and solutions

Background

Since its sudden appearance and link to microcephaly in 2015, the number of PubMed references for Zika virus (ZIKV) has risen from 181 to 5163, at time of writing, with a vast proportion focused on the consequences of ZIKV infection during pregnancy. This level of attention underlies increased demand for sensitive and specific diagnostic tools able to assess risk to an unborn child, as well as to understand the dynamics and consequences of viral persistence.

Effects of melanotan II,a melanocortin agonist,on grooming and exploration in rats after repeated restraint/immobilization

2 mg/kg melanotan II (MTII, administered i.p.), a cyclic peptide analog of α-melanocyte stimulating hormone, at a single dose increased grooming in naive rats placed in an unfamiliar open-field device without changing locomotion or rearing. Male rats exposed to restraint/immobilization stress (IS) for 1 h on three consecutive days displayed increased grooming after the second stressor exposure, compared to pre-stress levels. MTII, administered to the rats after IS, enhanced the grooming response compared both to the pre- and post-stress values. The increase was greatest after the first dose and declined over the following two applications. As to the locomotion of rats in the entire experimental space, IS reduced the distance moved only after the first two stressor exposures; MTII did not influence these alterations. Locomotion in the central part of arena was not reduced by the stressor or by MTII, on the contrary, there was an increase in both groups after the third intervention. The only observed change in rearing was an increase in the MTII group after the third restraint exposure. Thus, MTII selectively increased grooming without markedly affecting the spatio-temporal structure of locomotor behavior in the open-field. The decline of MTII enhanced grooming over the three test days may be interpreted in terms of adaptation to the stressor and of the developing tolerance to the peptide.     

Reliability and validity of the Biodex system 3 pro isokinetic dynamometer velocity,torque and position measurements

This study quantitatively assessed the mechanical reliability and validity of position, torque and velocity measurements of the Biodex System 3 isokinetic dynamometer. Trial-to-trial and day-to-day reliability were assessed during three trials on two separate days. To assess instrument validity, measurement of each variable using the Biodex System 3 dynamometer was compared to a criterion measure of position, torque and velocity. Position was assessed at 5° increments across the available range of motion of the dynamometer. Torque measures were assessed isometrically by hanging six different calibrated weights from the lever arm. Velocity was assessed (30°/s to 500°/s) across a 70° arc of motion by manually accelerating the weighted lever arm. With the exception of a systematic decrease in velocity at speeds of 300°/s and higher, the Biodex System 3 performed with acceptable mechanical reliability and validity on all variables tested.DisclosureThe Biodex dynamometer used for this investigation was donated to the laboratory by Biodex Medical Systems. The authors have no commercial or proprietary interest in this device.     

Apoptosis of ileal Peyer's patch B cells is increased by glucocorticoids or anti-immunoglobulin antibodies

The ileal Peyer's patch (PP) in sheep plays a central role in the development and production of B cells. Associated with a tremendous amount of B cell proliferation in this site is the extensive diversification of the Ig repertoire by somatic hypermutation. Very few (<5%) of the B cells produced in the ileal PP differentiate and emigrate; instead, the vast majority of these cells soon die, and we have previously shown that death is associated with apoptosis. When placed in culture, ileal PP B cells die rapidly by apoptosis, such that after 24h, 60 ± 1 % of DNA is fragmented. Here, we show that the extent of this spontaneous B cell apoptosis in culture, as quantitated by DNA fragmentation, was significantly increased in a dose-dependent manner by the glucocorticoids hydrocortisone or dexamethasone. Furthermore, treatment of lambs with 2–2.5 mg/kg of dexamethasone resulted in a marked increase in the number of apoptotic cells in the ileal PP and an increase in ileal PP B cell DNA fragmentation to 20 ± 6%, compared with 2.4 ± 0.1 % in untreated lambs. Anti-immunoglobulin (Ig) antibodies also increased the extent of DNA fragmentation in cultured ileal PP B cells. After 24 or 48 h of culture with anti-Ig (PIg47A), DNA fragmentation was 74 ± 2 % and 75 ± 3 %, respectively. Ileal PP B cells are rescued from apoptosis by agents that activate protein kinase C and increase cytosolic Ca²⁺, and here we show that this treatment also results in apoptotic rescue in the presence of dexamethasone or anti-Ig. We speculate that the apoptosis of ileal PP B cells in situ may be modulated by glucocorticoids and by the cross-linking of surface Ig. Apoptosis, induced by a signal through surface Ig, may be an important mechanism in the deletion of self-reactive B cells during the expansion of the Ig repertoire in the ileal PP.