Treatment of twin-reversed arterial perfusion sequence using high-intensity focused ultrasound.

We describe our experience of high-intensity focused ultrasound (HIFU) for fetal therapy in twin-reversed arterial perfusion (TRAP) sequence. Six pregnant women underwent HIFU therapy, five before 16 weeks and one at 26 weeks. Two types of HIFU system were used: the first-generation system, which comprised a biaxial transducer and continuous exposure pattern, and the second-generation system, which comprised a coaxial transducer and sequential exposure pattern. The first-generation apparatus was used in four cases and the second-generation apparatus was used in two. In three cases, occlusion of the blood vessels mediating flow to the acardiac twin was achieved by HIFU. Two cases experienced intrauterine fetal death despite vessel occlusion. The total survival rate of pump fetuses 2 years after HIFU was 67% and the efficiency rate (the proportion of cases with occlusion or reduced blood flow on ultrasound after HIFU) was 83%. After more than 2 years of follow-up, the surviving infants had no severe clinical complications and no postnatal developmental problems. There was no significant difference in survival rate compared with TRAP cases managed expectantly. Given that complete occlusion of the blood vessels was not achieved in half of the cases, we could not show that HIFU therapy is superior to other treatments. However, HIFU can reduce the cardiac load of the pump fetus and, as it does not require uterine puncture for fetal therapy, there were no fatal complications, such as bleeding, rupture of membranes or infection. Thus, HIFU therapy may represent a less-invasive treatment for TRAP sequence in early pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Influenza 2014-2015 among pregnant Japanese women: primiparous vs multiparous women.

This study was performed to determine whether multiparous pregnant women are prone to influenza. A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6,694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected. Seventy-eight percent (n = 51,97) of women given questionnaires responded. Of these, 2,661 (51 %) and 364 (7.0 %) women reported having been vaccinated and having contracted influenza respectively. Multiparous women had a higher risk of influenza regardless of vaccination status (8.9 % [121/1362] vs 5.7 % [74/1299], relative risk [95 % confidence interval], 1.80 [1.36 to 2.38] for vaccinated and 9.3 % [112/1198] vs 4.3 % [57/1328], 2.18 [1.60 to 2.97] for unvaccinated women) compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8 % (100/2089), 7.5 %, (121/1618), 9.0 %, (71/785), and 10.4 % (58/557) for women with 1, 2, 3, and ≥4 cohabitants respectively. Family size is a risk factor for influenza infection in pregnancy.

[Off-pump coronary artery bypass grafting as standard operation; surgical strategies and results].

We report the clinical results of 799 cases of isolated coronary artery bypass grafting (CABG) performed during the recent 5 years. We performed off-pump CABG (OPCAB) as standard operation, in which arterial grafts were mainly used. The mean number of distal anastomoses was 3.6 +/- 1.4 per patient Four hundred and fifty-five cases (57.0%) were done only with arterial grafts. Bilateral internal thoracic arteries were used in 326 cases. The mean number of saphenous vein grafts was 1.6 +/- 0.8 per patient. Continuous hemodiafiltraion (CHDF) was performed in 22 cases (2.8%) postoperatively. Among the OPCAB cases, 10 cases (1.3%) were converted to on-pump CABG. There were 7 cases (0.9%) of hospital death. The mean length of postoperative hospital stay was 10.2 +/- 5.3 days. The ratio of the patients with left main trunk disease and that of the patients who required postoperative CHDF increased year by year. The mean length of postoperative hospital stay decreased every year, and the reduced length was 2.7 days in the 5 years (8.7+/- 3.6 days in 2007). It is expected that patients who have severe calcified lesions or who are on hemodialysis may increase in the near future. In such cases, CABG rather than percutaneous catheter intervention may be suitable for revascularization. Therefore, not only appropriate choice of treatment strategies, but also accurate surgical techniques may become more importance.

Performance of the EuroSCORE II and the Society of Thoracic Surgeons Score in patients undergoing aortic valve replacement for aortic stenosis.

Aim. The aim of this study was to evaluate the performance of the new European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) score in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). This study also evaluated the performance of the EuroSCORE II in high-risk patients. Methods. Three hundred and six consecutive adult patients underwent AVR with or without coronary artery bypass grafting at our institution from August 2002 to June 2012. The cut-off value of 6% for the EuroSCORE II and 10% for the STS score was used to identify high-risk in this study. Results. Operative mortality was 3.5% (N.=11). The mean expected mortality for all patients was 3.1% (O/E ratio=1.12) for the EuroSCORE II and 5.1% (O/E ratio=0.68) for the STS score. Observed versus expected mortality for the high-risk patients was 17.2% versus 11.9% (O/E ratio=1.44) for the EuroSCORE II (N.=29) and 19.3% versus 18.5% (O/E ratio=1.04) for the STS score (N.=31), and that for the low-risk was 2.1% versus 2.2% (O/E ratio=0.95) for the EuroSCORE II and 1.8% versus 3.5% (O/E ratio=0.51) for the STS score. Discrimination power of the STS score was good (area under the receiver operating characteristics curve [AUC] 0.74), but that of the EuroSCORE II was suboptimal (AUC 0.66). Conclusion. Good calibration ability of the EuroSCORE II for low-risk patients and that of the STS score for high-risk are observed. However, the EuroSCORE II underestimates the operative mortality in high-risk patients and the STS score overestimates the risk in low-risk patients.

Age-related increase in systolic fraction of pulmonary vein flow velocity-time integral from transesophageal Doppler echocardiography in subjects without cardiac disease.

The pulmonary vein flow velocity-time profile would be equivalent to the pulmonary vein flow volume-time profile, provided that the cross-sectional area of the pulmonary vein remains unchanged during 1 cardiac cycle. The systolic fraction of the pulmonary vein flow velocity-time integral, a ratio of velocity-time integral of the S wave to the sum of velocity-time integrals of the S and D waves, represents the ratio of left atrial storage volume to left ventricular stroke volume. This systolic fraction may help early filling of the left ventricle through an appropriate storage of blood and generation of driving pressure in the left atrium. Because early filling of the left ventricle is progressively impaired with age, it was hypothesized that this systolic fraction is increased with age. Forty-four noncardiac surgical patients (age range 17 to 70 years) who underwent transesophageal Doppler echocardiography under general anesthesia were studied, and left upper pulmonary vein flow and mitral inflow velocities were recorded. The ratio of peak velocity of the E wave to that of the A wave of mitral inflow velocity-time profile (y) decreased with age (y = -0.0245 x age + 2.41; r = -0.672, p < 0.01). Systolic fraction (y) increased with age (y = 0.00373 x age + 0.514; r = 0.656, p < 0.01). The age-related increase in the systolic fraction of pulmonary vein flow velocity-time integral may account for the compensation for impaired early filling of the left ventricle in elderly patients.

Effects of local anesthetics on phospholipase D activity in differentiated human promyelocytic leukemic HL60 cells.

Local anesthetics impair certain functions of neutrophils, and phospholipase D (PLD) is considered to play an important role in the regulation of these functions. To understand the mechanisms by which local anesthetics suppress the functions of neutrophils, we examined the effects of local anesthetics on PLD in neutrophil-like differentiated human promyelocytic leukemic HL60 cells. Tetracaine, a local anesthetic, inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)- and 4beta-phorbol 12-myristate 13-acetate (PMA)-induced PLD activation, but potentiated fMLP-stimulated phospholipase C activity. All four local anesthetics tested suppressed PMA-induced PLD activation to different extents, and the order of their potency was tetracaine > bupivacaine > lidocaine > procaine. In a cell-free system, tetracaine suppressed guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-induced PLD activation as well as PMA-induced PLD activation. Western blot analysis revealed that tetracaine prevented the membrane translocation of PLD-activating factors, ADP-ribosylation factor, RhoA, and protein kinase Calpha. Tetracaine also inhibited the activity of recombinant hPLD1a in vitro. These results suggest that local anesthetics suppress PLD activation in differentiated HL60 cells by preventing the membrane translocation of PLD-activating factors, and/or by directly inhibiting the enzyme per se. Therefore, it could be assumed that local anesthetics would suppress the functions of neutrophils by inhibition of PLD activation.

Alteration of pulmonary oxygenation by pulmonary artery occluded pressure measurements in mechanically ventilated patients.

A significant decrease in PaO2 occurs in some patients during PAOP measurements. To examine the incidence and the types of patients whose PaO2 decreases during PAOP measurements, we studied the changes of PaO2 in 101 anesthetized, mechanically ventilated adult patients. During a 2-min inflation of a PAC balloon, seven patients (6.9 percent) developed marked decrease in PaO2/FIo2 (more than 100 mm Hg). Neither age nor size of patients, decrease in end-tidal CO2, nor baseline value of PAP correlated with the decreases in PaO2. A decrease in PaO2/FIo2 (more than 50 mm Hg) was observed more frequently in female patients and in patients with cardiac disease, especially those whose PAP values were above normal. Although a significant decrease in PaO2 during PAOP measurements does not appear to occur often, our results suggest that the changes in PaO2 should be evaluated in patients with severely compromised pulmonary oxygenation.

Comparison of two methods of postoperative respiratory care.

After abdominal surgery, 64 patients were managed with one of the following two techniques of respiratory care: (1) deep breathing by way of a new device, an incentive spirometric three-ball, flow-measuring device (Triflo); and (2) standard episodic intermittent positive-pressure breathing (IPPB) every four hours. Both series of patients received therapy with a bronchodilator drug by nebulization. All patients had preoperative spirometric measurements followed by five consecutive days of therapy and spirometry. Chest x-ray films were obtained for all patients. There were no significant differences between the two methods of respiratory care, but 57 percent (17/30) in the group receiving therapy with IPPB developed pneumonia, atelectasis, or bronchitis, while only 29 percent (10/34) did so in the group using the incentive spirometric device (P less than 0.05). Spirometric differences were minimal, although the trend favored the incentive spirometric device. Principal conclusions were as follows: (1) deep breathing under the conditions of this investigation was equal to episodic therapy with IPPB; and (2) from an economic standpoint, IPPB, as it is currently practiced, may be disadvantageous when compared with the incentive spirometric device.

Mitral prosthetic dehiscence with laminar regurgitant flow signals assessed by transesophageal echocardiography.

A patient with a Björk-Shiley mitral prosthesis developed progressive heart failure without heart murmur and hemolysis. The prosthetic dehiscence was not diagnosed using transthoracic echocardiography, but transesophageal echocardiography. The regurgitant signals revealed laminar flow pattern with large regurgitant orifice. In patients with mitral prosthetic dehiscence with laminar flow pattern, transesophageal echocardiography can provide reliable diagnostic information.

Non-GABAergic effects of midazolam, diazepam and flumazenil on voltage-dependent ion currents in NG108-15 cells.

Non-gamma-Aminobutyric acid (GABA)-mediated effects of benzodiazepines (BZs) have not been widely investigated. However, there is significant evidence in the literature to suggest that several experimental and clinical observations are inconsistent with the commonly accepted GABAergic mechanisms of action for these drugs. The purpose of the present study was to explore electrophysiological effects of midazolam, diazepam and a specific BZ antagonist, flumazenil, using patch-clamp techniques in NG108-15 cells which do not express the GABAA receptor. Midazolam and diazepam decreased Na+, K+ and Ca2+ currents in a dose-related manner. Ca2+ currents were reduced more significantly by diazepam than by midazolam. Flumazenil showed no effects on voltage-dependent ion currents. GABA by itself showed neither effects on the membrane potential nor these ion currents. Midazolam and diazepam, but not flumazenil, exhibited effects on voltage-dependent ion currents in cultured neurons.

Heterogeneity in the molecular species of heat-stable enterotoxin of Vibrio cholerae non-O1 expressed by Escherichia coli carrying the cloned toxin gene.

The biological activity of the heat-stable enterotoxin of Vibrio cholerae non-O1 (NAG-ST) was found to be predominantly associated with the periplasmic extract (about four-fold higher than the culture supernatant) of a recombinant E. coli (JM109) strain carrying the NAG-ST toxin gene. Four molecular species of NAG-ST, two each from the periplasmic extract and culture supernatant of JM109, were purified. Amino acid sequence analysis of the four NAG-ST peptides isolated by HPLC revealed that they all differed from that of the mature 17-amino acid residue NAG-ST released by V. cholerae non-O1. The M(r)-values of the peptides obtained from the periplasmic extract were 4331 and 2785, while those recovered from the culture supernatant were 3154 and 2785. It thus appears that V. cholerae NAG-ST is synthesized as larger molecules in the recombinant E. coli strain. The differences in sizes of the exported NAG-ST molecule could relate to differences in the enzyme cleavage system between E. coli and V. cholerae.

Detection of heat-stable enterotoxin in a cholera toxin gene-positive strain of Vibrio cholerae O1.

DNA colony hybridization with a polynucleotide clonal DNA probe for heat-stable enterotoxin of Vibrio cholerae non-O1 (NAG-ST) was used to screen 197 isolates of V. cholerae O1. Under stringent hybridizing and washing conditions, one strain (GP156) reacted with the probe. The concentrated supernatant from V. cholerae O1 GP156, heated at 100 degrees C for 5 min, elicited fluid accumulation in the suckling mice and that could be completely neutralized by an anti-NAG-ST monoclonal antibody (mAb2F). The preparation from V. cholerae O1 GP156 also inhibited the binding of mAb2F to NAG-ST in a competitive ELISA. V. cholerae O1 GP156 was confirmed to possess a gene encoding cholera toxin (CT). These results indicate that a heat-stable enterotoxin is produced by certain strains of CT-producing V. cholerae O1.

Engraftment of precursor lesions of human cutaneous neoplasms onto C.B-17 SCID mice: a useful in vivo experimental model of carcinogenesis in human skin.

Using a full-thickness skin grafting technique, lesional skin from various human neoplastic and preneoplastic skin diseases was transplanted onto SCID (severe combined immunodeficiency) mice. Of 27 grafted lesions, 21 were successfully accepted by the mice and maintained in good condition. All these accepted grafts were finally excised 10-101 days after transplantation for histological examination. In most grafts, the characteristic histological configurations of each disease were well preserved. Immunohistochemical study using monoclonal antibodies to human blood group antigens ABH revealed that some elements of the grafts such as sweat glands were clearly positive, confirming that the tissue was from human skin. Neoplastic (atypical) cells were detected in 9 of 17 accepted grafts containing neoplastic cells from the beginning. The detection rates for neoplastic cells were very high (90%) in grafts from precursor lesions of squamous cell carcinomas such as Bowen's disease (5/5 specimens) and thermal keratosis (2/3). In contrast, no definite neoplastic cells were found in two grafts from extramammary Paget's disease and five grafts from the radial growth component of malignant melanoma. In most of the grafts from latter two diseases, characteristic histological configurations such as elongation of the rete ridges were maintained, suggesting that the neoplastic cells were selectively eliminated from the grafts. Split-thickness grafts of normal human skin were accepted and remained in a good condition for as long as 6 months. Engraftment of human lesional and non-lesional skin onto SCID mice therefore may well provide a useful in vivo experimental model of human skin diseases.

New immunodeficient (nude-scid, beige-scid) mice as excellent recipients of human skin grafts containing intraepidermal neoplasms.

Engraftment of normal or lesional human skin onto nude or SCID (severe combined immunodeficiency) mice has been used as an in vivo experimental model. However, this model has some limitations, such as shrinkage and loss of the grafted skin over time. To improve the experimental model, we have produced two new SCID-lineage mouse strains, BALB/cA-nude-scid (nu/nu, scid/scid) and BALB/cA-beige-scid (bg/bg, scid/scid) mice, by the method of cross intercross. Intraepidermal neoplastic lesions such as Bowen's disease were grafted onto the back of the mice of these strains. The rate of reduction in the size of the grafts was lower on nude-scid and beige-scid mice than on SCID mice. Rates of survival of neoplastic cells in the grafts were higher in nude-scid mice than in SCID and beige-scid mice (SCID mice 38%, nude-scid mice 55%, beige-scid mice 38%). Neoplastic cells of Bowen's disease grafted onto a beige-scid mouse proliferated and invaded the dermis during 233 days of observation, confirming the progression to invasive squamous cell carcinoma from carcinoma in situ. The present study revealed that nude-scid and beige-scide mice newly produced by us provide a very useful in vivo experimental model for the investigation of carcinogenesis and tumor progression in human skin.

Biological assessment of the enhancement of tritium excretion by administration of diuretics and excessive water in mice.

This study was undertaken to determine whether or not the administration of diuretics and excess water after tritium exposure would have any positive reducing effect not only on the retention of tritium but also on the radiation damage of hematopoietic tissue in mice. When mice were treated with diuretics and excess water for a few days after injection of tritiated water (HTO), radioactivity within the body fluid and tissues was reduced, and the number of CFU-s, clonability of splenic T cells and proliferative activity assayed by Con-A blastogenesis were increased in comparison with those in the controls. When the mice were injected with a large dose of HTO (811 MBq/mouse) to assay survival, no mice treated with diuretic and excess water died 80 days after injection, while 80% of the controls died during the first month. The final committed dose in the mice treated early with diuretics was calculated to be 60% of that in the controls. These results suggest that treatment with diuretics and excess water is useful for practical purposes when a human is accidentally exposed to tritium.

Clonidine premedication reduces maternal requirement for intravenous morphine after cesarean delivery without affecting newborn's outcome.

BACKGROUND AND OBJECTIVES: The alpha(2)-agonist clonidine has several benefits for patients undergoing surgery. During and after elective cesarean delivery (C-section), we assessed the condition of parturient and neonate when one half of the parturients were pretreated with oral clonidine. METHODS: Forty-six consenting parturients were studied in a randomized, double-blinded manner. Preanesthetic medication was atropine and famotidine with or without clonidine 4 microg/kg. After baseline measurements in parturients and fetuses, combined spinal and epidural anesthesia was established (1.6 mL of 0.5% tetracaine diluted with 10% dextrose in water). C-section was performed while breathing oxygen spontaneously (3 L/min) through a facemask. After delivery, neonates were assessed at 1 and 5 minutes, and the condition of mother and neonate was observed for 48 hours. RESULTS: Parturients receiving clonidine showed no hemodynamic instability during and after C-section, and while their visual analog scale (VAS) scores, verbal descriptive scale (VDS) scores, and sedation scores did not differ from those without clonidine, they needed significantly less patient-controlled analgesia (PCA) morphine for postoperative pain for the first 2 days (P < .01). Fetal heart rate, umbilical artery and vein pH and gas tensions, and the Apgar-scores of the newborns showed no intergroup differences. No neonatal depression or bradycardia was observed for 48 hours after delivery. CONCLUSION: The present results indicate that oral clonidine reduces the PCA morphine requirement after C-section without compromising the condition of the fetus or newborn. Further study including larger number of patients would be needed before we conclude that oral clonidine for parturients is safe for their newborns.

Prediction of patients with higher order multifetal pregnancy at risk for postpartum pulmonary edema.

OBJECTIVE: This retrospective study aims to verify the factors for the development of maternal pulmonary edema in higher order multifetal pregnancy. STUDY DESIGN: We analyzed medical profiles of a total of 13 triplet, quadruplet and quintuplet pregnancies for the years 1992 through 1997. Some treatments were applied in attempts to promote these multifetal pregnancies. All underwent cesarean section, two of which developed pulmonary edema within a few hours of delivery. There had been no evidence for the development of pulmonary edema antepartum. RESULTS: In the patients affected by pulmonary edema, postoperative values of PaO2/FIO2<250 mmHg showed close association to a value perioperative fluid loading index (FLI)>0; the index consists of an intraoperative fluid balance and preoperative infusion volume within 24 h prior to surgery. Two patients with postoperative pulmonary edema had a perioperative FLI>0, whereas the others had values 0 may have a much higher risk for postoperative pulmonary edema, suggesting the predictive role of the perioperative FLI value.

Nonrespiratory rhythmic fluctuations in systemic arterial pressure in anesthetized humans.

STUDY OBJECTIVE: To clarify the frequency of nonrespiratory rhythmic fluctuations in systemic arterial pressure (vasomotor waves) and to identify the clinical conditions in which the vasomotor waves develop in humans under anesthesia. DESIGN: Retrospective analysis of collected data. SETTING: Inpatient surgery clinic at a university hospital. PATIENTS: Five hundred thirteen consecutive ASA physical status II-V patients. INTERVENTIONS: Direct arterial pressure monitoring and general anesthesia, including high-dose fentanyl, enflurane, enflurane plus fentanyl, cervical or thoracic epidural, and lumbar epidural anesthesia. MEASUREMENTS AND MAIN RESULTS: Among the anesthesia techniques used, vasomotor waves occurred most frequently in patients anesthetized with high-dose fentanyl (31.1%) and least frequently in those with high-level epidural blockade (7.4%). As a result of multiple logistic analysis, the contributing factors to the appearance of vasomotor waves were the institution of cardiopulmonary bypass (CPB) and the patient's age. It is also a novel finding that nearly one-third of the vasomotor waves developed in patients under stable hemodynamic conditions. CONCLUSIONS: Vasomotor waves are a common phenomenon in relatively high-risk patients during general anesthesia. The appearance of vasomotor waves is significantly related to CPB and patient age.

Ketamine, not propofol, attenuates cerebrovascular response to carbon dioxide in humans with isoflurane anesthesia.

STUDY OBJECTIVES: To investigate the effects of ketamine and propofol on the cerebrovascular response to carbon dioxide (CO(2)) in humans during isoflurane anesthesia. DESIGN: Randomized clinical investigation. SETTINGS: University hospital of a medical school. PATIENTS: 30 ASA physical status I and II adult, elective surgical patients. INTERVENTIONS AND MEASUREMENTS: With each patient given air/oxygen/isoflurane anesthesia, the flow velocity in the middle cerebral artery (Vmca) and pulsatility index were measured using the transcranial Doppler method under hypocapnic [arterial CO(2)tension (PaCO(2)) 28-32 mmHg], normocapnic (PaCO(2) 38-42 mmHg), and hypercapnic conditions (PaCO(2) 48-52 mmHg). PaCO(2) was altered by supplementing the inspired gas with CO(2) without changing the respiratory conditions. Patients were then randomly assigned to receive either ketamine 1 mg. kg(-1) or propofol (2 mg. kg(-1)followed by an infusion of 6-10 mg. kg(-1). hr(-1)) (n = 15 for each drug), and the measurements were repeated. MAIN RESULTS: Ketamine reduced both absolute and relative cerebrovascular reactivity to CO(2) significantly [2.9 +/- 0.8 (control) vs. 2.6 +/- 1.0 (ketamine) cm. sec(-1). mmHg(-1): p < 0.05; and 3.5 +/- 0.7 (control) vs. 2.8 +/- 0.9 (ketamine) %. mmHg(-1): p < 0.01, respectively]. However, ketamine did not reduce Vmca during hypercapnic conditions (117 +/- 29 cm. sec(-1)) compared with controls (120 +/- 28 cm. sec(-1)). Although propofol decreased Vmca during all conditions, it did not cause any change in either absolute or relative CO(2) reactivity [2.5 +/- 0.8 (control) vs. 2.5 +/- 1.0 (propofol) cm. sec(-1). mmHg(-1), and 3.3 +/- 1.3 (control) vs. 4.1 +/- 1.0 (propofol) %. mmHg(-1), respectively]. CONCLUSIONS: In humans given isoflurane anesthesia, a) ketamine reduced cerebrovascular response to CO(2), but cerebral blood flow (CBF) during hypercapnic conditions was comparable with controls, and b) although propofol decreases CBF, it maintains the cerebrovascular response to CO(2).