Technical Performance and Reflection Capacity of the Anaesthetic Conserving Device—A Bench Study with Isoflurane and Sevoflurane

Objective

The anaesthetic conserving device (AnaConDa^®, Sedana Medical, Sundbyberg, Sweden) facilitates administration of isoflurane or sevoflurane by liquid infusion. An anaesthetic reflector inside the device conserves exhaled anaesthetic and re-supplies it during inspiration. In this bench study, we examined the influence of infusion rates and ventilatory settings on the resulting anaesthetic concentrations on patient (C_pat) and ventilator side of the reflector (C_loss) to describe its technical performance.

Methods

A Puritan Bennett 840 ICU ventilator (Pleasanton, US), AnaConDa^®, and a test lung (3 l-chloroprene-bag) were assembled. Infusion rates (IR, 0.2-50 ml h^-), respiratory rates (RR, 5-40 breaths min^-1), and tidal volumes (V_T, 0.3, 0.5, and 1.0 l) were varied. C_pat was measured via a thin catheter in the middle of the 3 l-bag in steady state (online data storage and averaging over >10 min). C_loss was calculated from IR (to yield the volume of vapour per unit of time), and expired minute volume (in which the vapour is diluted) on the assumption that, in the steady state, input by liquid infusion equals output through the reflector.

Results

At lower concentrations (C _pat< 1 vol%) the ratio C_loss/C_pat was constant (R _C = 0.096?±±0.012) for all combinations of IR, RR and V_T, both for isoflurane and sevoflurane. The device could efficiently reflect up to 10 ml vapour per breath (e.g. 2 vol% in 0.5 l). When exceeding this capacity, surplus vapour “spilled over” and R_C markedly increased indicating decreased performance.

Conclusions

The triple product minute volume times R_C times C_pat describes anaesthetic losses through the reflector. It can easily be calculated as long as the 10 ml reflection capacity is not exceeded and thus R_C is constant. Increased minute ventilation necessitates increasing the IR to keep C_pat constant. When using large V_T and high C_pat “spill over” occurs. This effect offers some protection against an inadvertent overdose.     

Assessment of Relationship of Serum Neurokinin-B Level in the Pathophysiology of Pre-eclampsia: A Case–Control Study

Introduction

Pre-eclampsia is a pregnancy-induced disorder that complicates approximately 5–7% of pregnancies. It is the leading cause of maternal and foetal morbidity and mortality worldwide.

Aim

To determine the role of serum neurokinin-B level in the pathophysiology of pre-eclampsia.

Methods

This was a case–control study. A total of 80 pregnant women in their third trimester of pregnancy were included in the study. They were divided into two groups (40 pre-eclamptic and 40 normotensive) according to the presence or absence of clinical parameters of pre-eclampsia. Serum level of neurokinin-B was measured with ELISA.

Results

Maternal age, weight, BMI, pulse, systolic BP and diastolic BP were statistically higher in the pre-eclampsia group compared to the normotensive group (P?<?0.0001). Moreover, statistically higher levels were observed for neurokinin-B in the normotensive group as compared to the pre-eclamptic group. The mean value of neurokinin-B was 83.50 ng/L in the pre-eclamptic group compared to 111.5 ng/L in the normotensive group (P?=?0.006).

Conclusion

Higher levels of serum neurokinin-B were observed in the normotensive pregnant females as compared to the pre-eclamptic females. Thus, apparently, it seems that serum neurokinin-B plays no role in the pathophysiology of pre-eclampsia, and further large multicentre prospective studies may be required to ascertain its role.

     

Effect of Restoration of AV Synchrony on Stroke Volume,Exercise Capacity,and Quality‐of‐Life: Can We Predict the Beneficial Effect of a Pacemaker Upgrade?

The aim of this study was to assess to what extent patients with VVIR pacemakers and without overt symptoms of a pacemaker syndrome benefit from a pacemaker upgrade, and if a preoperative noninvasive measurement of the change in stroke volume (SV) could predict the effect of a pacemaker upgrade. The study group consisted of 20 (12 women, 8 men) VVIR patients with a mean age of 60 years. The indication for the first implantation was AV block in 13 patients and SSS in 7. The mean time of a ventricular pacing was 77 months. The objective (echocardiography, an exercise capacity) and the subjective (the quality-of-life) parameters investigated in patients during ventricular pacing were compared to results obtained 2 months and 1 year after a pacemaker upgrade. To assess preoperatively a change in a SV expected after upgrading, attempts were made to restore AV synchronization by the use of a transesophageal pacemaker. An increase in SV (from 5% to > 35%) during temporary AV resynchronization was observed in each patient. Values of SV increase correlated with those obtained 2 months (r = 0.65; P < 0.01) and 1 year (r = 0.66; P < 0.01) after an upgrade. Superior hemodynamics was associated with a significant improvement of an exercise capacity in both subgroups of patients. The most significant improvement in the quality-of-life was observed in patients with SSS. We did not find correlations between SV and the quality-of-life assessed 2 months (r = 0.043; NS) or 1 year (r = 0.02; NS) after an upgrade. In conclusion, a pacemaker upgrade performed after a long-term ventricular pacing resulted almost consistently in the improvement of hemodynamics and was associated with an increase of exercise capacity. In patients with SSS it was followed by the significant improvement of their quality-of-life. Such a relation was not observed in patients with AV block as some of them (especially those with VVIR pacemakers) felt quite well during ventricular pacing. The proposed preoperative echocardiographic evaluation may precisely predict the degree of hemodynamic improvement expected after a pacemaker upgrade.     

Mechanisms of the Antitumor Activity of Human Vγ9Vδ2 T Cells in Combination With Zoledronic Acid in a Preclinical Model of Neuroblastoma

Low expression of surface major histocompatibility complex (MHC) class I molecules and defects in antigen processing machinery make human neuroblastoma (NB) cells appropriate targets for MHC unrestricted immunotherapeutic approaches. Human T-cell receptor (TCR) Vγ9Vδ2 lymphocytes exert MHC-unrestricted antitumor activity and are activated by phosphoantigens, whose expression in cancer cells is increased by aminobisphosphonates. With this background, we have investigated the in vivo anti-NB activity of human Vγ9Vδ2 lymphocytes and zoledronic acid (ZOL). SH-SY-5Y human NB cells were injected in the adrenal gland of immunodeficient mice. After 3 days, mice received ZOL or human Vγ9Vδ2 T cells or both agents by intravenous administration once a week for 4 weeks. A significantly improved overall survival was observed in mice receiving Vγ9Vδ2 T cells in combination with ZOL. Inhibition of tumor cell proliferation, angiogenesis and lymphangiogenesis, and increased tumor cell apoptosis were detected. Vγ9Vδ2 T lymphocytes were attracted to NB-tumor masses of mice receiving ZOL where they actively modified tumor microenvironment by producing interferon-γ (IFN-γ), that in turn induced CXCL10 expression in NB cells. This study shows that human Vγ9Vδ2 T cells and ZOL in combination inhibit NB growth in vivo and may provide the rationale for a phase I clinical trial in patients with high-risk NB.     

Effects of Physical Exercise Interventions on Dual–Task Gait Speed Following Stroke: A Systematic Review and Meta–Analysis

Objectives

To estimate the treatment effects of exercise and/or gait training interventions on dual–task walking in people with stroke. The secondary objective was to conduct subgroup analyses to compare the treatment effects of interventions involving dual–task training to those without any dual–task training.

Study Design of VESUTO<Superscript>®</Superscript>: Efficacy of Tiotropium/Olodaterol on Lung Hyperinflation,Exercise Capacity,and Physical Activity in Japanese Patients with Chronic Obstructive Pulmonary Disease

Introduction

The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD.

Methods

A protocol is developed for the VESUTO^® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD.

Results

A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT^® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints.

Conclusion

The VESUTO^® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting β₂-agonist (LABA) combination therapy on patients’ physical activities as well as lung function.

Trial registration

ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015).

Funding

The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.

     

Effectiveness of Client-Centered “Tune-Ups” on Community Reintegration,Mobility, and Quality of Life After Stroke: A Randomized Controlled Trial

Objective

To explore the effectiveness of a 2-week client-centered rehabilitation intervention (tune-up) delivered 6 months after inpatient discharge on community reintegration at 1 year in people with stroke.

Metabolism in Human Cells of the d and l Enantiomers of the Carbocyclic Analog of 2′-Deoxyguanosine: Substrate Activity with Deoxycytidine Kinase,Mitochondrial Deoxyguanosine Kinase,and 5′-Nucleotidase

The carbocyclic analog of 2′-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because of recent observations with other nucleoside analogs that biological activity may be associated the l enantiomer rather than, as expected, with the d enantiomer, we have studied the metabolism of both enantiomers of CdG to identify the enzymes responsible for the phosphorylation of CdG in noninfected and virally infected human and duck cells. We have examined the enantiomers as substrates for each of the cellular enzymes known to catalyze phosphorylation of deoxyguanosine. Both enantiomers of CdG were substrates for deoxycytidine kinase (EC 2.7.1.74) from MOLT-4 cells, 5′-nucleotidase (EC 3.1.3.5) from HEp-2 cells, and mitochondrial deoxyguanosine kinase (EC 2.7.1.113) from human platelets and CEM cells. For both deoxycytidine kinase and mitochondrial deoxyguanosine kinase, the l enantiomer was the better substrate. Even though the d enantiomer was the preferred substrate with 5′-nucleotidase, the rate of phosphorylation of the l enantiomer was substantial. The phosphorylation of d-CdG in MRC-5 cells was greatly stimulated by infection with human cytomegalovirus. The fact that the phosphorylation of d-CdG was stimulated by mycophenolic acid and was not affected by deoxycytidine suggested that 5′-nucleotidase was the enzyme primarily responsible for its metabolism in virally infected cells. d-CdG was extensively phosphorylated in duck hepatocytes, and its phosphorylation was not affected by infection with duck hepatitis B virus. These results are of importance in understanding the mode of action of d-CdG and related analogs and in the design of new biologically active analogs.d-CdG is an analog of CdG that has broad-spectrum antiviral activity (27–29). Until recently, the biological activity of a nucleoside analog was assumed to be due only to the “natural” β-d form. However, there are now numerous observations of antiviral activity associated with nucleosides in l configurations (for reviews, see references 10 and 26) and one report of antitumor activity associated with a β-l enantiomer (11). Even though l-CdG is much less active against HSV (4) and HCMV (unpublished results), it is essential that the metabolism of both enantiomers be examined to thoroughly understand the mechanism of action of a nucleoside analog. We have reported earlier that both enantiomers of CdG are extensively phosphorylated in cells infected with HSV-1 and that the enantiomers had equal activities as substrates for the virus-encoded kinase (4, 5). It was also observed that d-CdG was converted to its triphosphate (but to a much lesser extent) in noninfected cells and that more than one enzyme appeared to be involved in the initial phosphorylation. Since cellular enzymes presumably are responsible for the activation of CdG in cells infected with HBV (which is not known to code for a kinase) and may also be important for the activation of CdG in cells infected with HCMV (which induces cellular kinases [6, 8, 21, 23, 32, 44], in addition to encoding a ganciclovir-phosphorylating enzyme [22, 35]), we have evaluated the enantiomers of CdG as substrates for the three cellular enzymes known to catalyze phosphorylation of deoxyguanosine (2): dCyd kinase, mitochondrial dGuo kinase, and 5′-nucleotidase. We also report here observations on the metabolism of d-CdG in cells infected with HCMV and in duck hepatocytes infected with DHBV.(Some of these results have been presented elsewhere in preliminary form [1].)     

Evaluating a Bereavement Follow-Up Intervention for Grieving Fathers and Their Experiences of Support After the Death of a Child—A Pilot Study

This article describes a study designed to evaluate the effectiveness of an intervention program for bereaved fathers and their experiences of it in a sample of intervention (n = 62) and control (n = 41) fathers. Data were collected by 3 scales: the Hogan Grief Reactions Checklist, a scale for measuring received social support, and a scale for measuring fathers' experiences of the intervention program. Assessment at 6 months after leaving the hospital showed that intervention fathers reported lower grief reaction scores and stronger personal growth. Intervention fathers reported the most emotional support from both health care personnel and peer supporters. The support received was perceived as helpful in coping, and fathers rated the intervention favorably. The findings support the continuation of the intervention.     

Tai Chi Exercise can Improve the Obstacle Negotiating Ability of People with Parkinson’s Disease: A Preliminary Study

[Purpose] The purpose of this study was to examine the effects of Tai Chi (TC)-based exercise on dynamic postural control during obstacle negotiation by subjects with mild or moderate Parkinson’s disease (PD). [Subjects] Twelve subjects (mean age, 65.3±6.1 years) diagnosed with idiopathic PD were enrolled for this study. [Methods] All the subjects were tested a week before and 12 weeks after the initiation of the TC exercise. In the test, they were instructed to negotiate an obstacle from the position of quiet stance at a normal speed. They were trained with TC exercise that emphasized multidirectional shift in weight bearing from bilateral to unilateral support, challenging the postural stability, three times per week for 12 weeks. Center of pressure (COP) trajectory variables before and after TC exercise were measured using two force plates. [Results] A comparison of the results between pre- and post-intervention showed a statistically significant improvement in anteroposterior and mediolateral displacement of COP. [Conclusion] Twelve weeks of TC exercise may be an effective and safe form of stand-alone behavioral intervention for improving the dynamic postural stability of patients with PD.Key words: Obstacle negotiation, Parkinson’s disease, Tai Chi exercise     

Cardiorespiratory Fitness and the Risk of Serious Ventricular Arrhythmias: A Prospective Cohort Study

Cardiorespiratory fitness (CRF) is an established risk factor for cardiovascular disease outcomes. However, the relationship of CRF with risk of ventricular arrhythmias (VAs) is unknown. We aimed to assess the prospective association of CRF with the risk of serious VAs. Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed using a respiratory gas exchange analyzer in 2299 middle-aged men in the Kuopio Ischemic Heart Disease prospective cohort. We corrected for within-person variability in CRF levels using data from repeated measurements 11 years apart. During median follow-up of 25.3 years (interquartile range, 18.7-27.2 years), 73 serious VAs were recorded. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI, 0.53-0.64). In analysis adjusted for age, the hazard ratio (HR) for serious VAs per 1-SD increase in CRF was 0.64 (95% CI, 0.49-0.84). The association persisted on additional adjustment for body mass index, systolic blood pressure, history of hypertension, prevalent coronary heart disease, smoking, history of diabetes, cholesterol level, alcohol consumption, and physical activity (HR, 0.67; 95% CI, 0.51-0.88). The corresponding adjusted HRs (95% CIs) were 0.29 (0.14-0.59) and 0.32 (0.15-0.65), respectively, comparing the top vs bottom tertiles. The associations were stronger on correction for regression dilution bias, remained consistent on exclusion of men with a history of coronary heart disease, and did not vary importantly in several relevant clinical subgroups. Cardiorespiratory fitness is inversely associated with future risk of serious VAs, independently of several cardiovascular disease risk factors. Further research is needed to assess the causal relevance of these findings.     

Proposed Bedside Maneuver to Facilitate Accurate Anatomic Orientation for Correct Positioning of ECG Precordial Leads V1 and V2: A Pilot Study

Background

Misplacement of right precordial electrocardiogram (ECG) electrodes superiorly is a prevalent procedural error that may lead to false findings of T-wave inversion or QS complexes in V2—possibly triggering wasteful utilization of health care resources. Standard technique for proper placement of V1–V2 entails initial palpation for the sternal angle, pointing to the second intercostal space (ICS), followed by lead fixation at the fourth ICS.

Study Objective

Because adherence to this approach may be limited by lack of a visual landmark for the second ICS, we assessed an alternative technique.

Methods

The evaluated technique involved placement of the patient’s hand up against the base of his/her neck (H→N maneuver) to help demarcate visually a specific point “X” on the chest.

Results

Of 112 patients studied, “X” landed on the first rib in 2.7%, first ICS in 7.1%, second rib in 56.3%, second ICS in 33.0%, and third rib in 0.9%. Thus, in 89.3% (95% confidence interval 83.6–95.0%) of cases (93.3% of men, 84.6% of women; p = 0.13), the second ICS could be identified by H→N via the following simple rule: Utilize “X” if it overlies an ICS; or the immediately subjacent ICS if “X” overlies a rib.

Conclusion

The H→N maneuver provides a primarily visual approach to identifying the second ICS and, thereby, the fourth ICS for affixing V1–V2. If the present initial experience is confirmed, H→N might merit consideration as an educational tool to promote anatomically correct placement of these precordial leads, a prerequisite to diminishing the incidence of ECG procedure-related “septal ischemia/infarction.”     

A Cross-cultural Test of the Cognitive Theory of Obsessions and Compulsions: A Comparison of Greek, Italian, and American Individuals—a Preliminary Study

A widely-held theory is that obsessions arise from the misinterpretation of normal intrusive thoughts (e.g., misinterpreting unwanted harm-related thoughts as a sign that one is going to act on them). This leads the person to perform compulsions such as repeated checking. Misinterpretations are said to arise from various types of beliefs (e.g., the belief that thoughts inevitably give rise to actions). In support of this theory, some studies have shown that such beliefs are correlated with obsessive-compulsive (OC) symptoms. We investigated whether the theory can be extended to conditions in which cultural differences are taken in consideration. Measures of OC beliefs and symptoms were completed by participants in Greece (n = 46) and Italy (n = 348) and, for comparison purposes, the US (n = 73). Beliefs were correlated with symptoms in all three groups. There were significant, albeit modest, cross-cultural effects. In particular, the relation between beliefs and cleaning and checking compulsions tended to be low in Greek participants, compared to Italian and US counterparts. Although the results generally support the cognitive model, some culture-specific modifications may be required, possibly by including variables that moderate or attenuate the correlations between OC symptoms and putatively related beliefs.