Integral Pulse Frequency Modulated Ultrasound for the Detection and Quantification of Gas Microbubbles in Flowing Blood

Perfusion ◽  
1987 ◽  
Vol 2 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Gordon Wright ◽  
Anthony Furness ◽  
Susan Haigh

An integral pulse frequency modulated gas microbubble detector is described. When used in conjunction with an electromagnetic blood flowmeter, the ultrasound pulse repetition frequency can be regulated to reduce multiple counting errors due to variations in blood flow rate. A special detector mounting head eliminates problems due to wall curvature and pulsation, permits reliable and reproducible transducer coupling and makes it possible to gate the ultrasound field electronically in order to avoid spurious counts due to crystal and wall artefacts and low intensity regions. Results obtained from the detector during an in vitro evaluation of bubble oxygenators suggest that the number of arterial line gas microbubbles is less than has been claimed previously and that the total volume of gas liberated in the form of microbubbles may be too small to have any demonstrable primary clinical effects.

1998 ◽  
Vol 21 (9) ◽  
pp. 535-541 ◽  
Author(s):  
G.B. Fiore ◽  
G. Pennati ◽  
F. Inzoli ◽  
F. Mastrantonio ◽  
D. Galavotti

The clinical advantages achievable through pulsatile blood perfusion during cardio-pulmonary bypass have recently suggested the design of new pulsatile systems for extracorporeal circulation. Still it is not clear whether current commercial membrane oxygenators could be adopted with such systems, since their behaviour with pulsatile perfusion has not been satisfactorily documented yet. In a previous paper, we assessed that pulsatile perfusion of a widely used hollow fibre oxygenator (Sorin® Monolyth) at 60 bpm provides more time-consistent oxygen transfer than steady perfusion. The present work is aimed to evaluate how the pulse frequency influences the gas transfer performance of the same device. The oxygenator was subjected to in vitro trials using a roller pump with pulsatile module (Stöckert Instrumente®) to generate pulsed flow. Four different pulse frequencies (45, 60, 75 and 90 bpm) were investigated at a fixed blood flow rate (4.0 l/min). The experiments lasting six hours were carried out using bovine blood with inlet conditions according to AAMI standards requirements. Blood samples were withdrawn every hour and O2 and CO2 transfer rates were evaluated. The experimental findings confirm that with pulsatile blood flow no time decay take place during prolonged perfusion. Moreover, when pulse frequency increases, transition levels occur for both O2 and CO2. Over these thresholds gas transfer rates display significant increases (p < 0.05), though of little magnitude (up to 2.5% for oxygen over 60 bpm; up to 3.7% for carbon dioxide over 75 bpm).


1987 ◽  
Vol 130 (1) ◽  
pp. 87-106
Author(s):  
ROBERT E. SHADWICK ◽  
JOHN M. GOSLINE ◽  
WILLIAM K. MILSON

Simultaneous measurements of blood pressure and blood flow were made in the dorsal aorta of the cephalopod Octopus dofleini Wülker. In resting animals the heart rate varied from 8.5 to 14 beats min−1, while aortic pressure typically ranged from about 2.5 kPa at end diastole to 5.5 kPa at peak systole. Blood flow rate varied with pressure, averaging 0.9 ml s−1, with peak flow rates of 1.4–2.8 ml s−1. A slow asymptotic decline in both pressure and flow during the 2- to 4-s diastolic period indicated that the aorta functions as an elastic reservoir, as previously predicted. Aortic impedance spectra were derived from digitized pressure and flow data. The impedance amplitude decreased continuously with increasing frequency, while the impedance phase was always negative. These results are consistent with a two-element Windkessel model of the arterial system. The apparent pressure wave velocity, determined from transit times of pressure pulses in vivo, was &gt; 10 m s−1. This was much higher than the intrinsic wave velocity we predicted from in vitro measurements of aortic elasticity. This anomaly occurred because the length of the aorta represented less than 1 % of the wavelength of the fundamental pulse frequency, due to the low heart rate in this species. Consequently, arterial haemodynamics in O. dofleini are dominated by strong wave reflections, but do not exhibit other wave propagation effects which are typical of mammalian circulatory systems. Thus, the simple Windkessel model adequately describes the arterial circulation of this species of cephalopod.


1973 ◽  
Vol 30 (01) ◽  
pp. 138-147 ◽  
Author(s):  
Christopher R. Muirhead

SummaryThe filter loop technique which measures platelet aggregation in vivo in the flowing-blood of the rat was compared to the optical density technique of Born which is carried out in vitro with platelet rich plasma. Using these two experimental models the effect on platelet aggregation of three known inhibitors sulfinpyrazone, dipyridamole and prostaglandin E1, and a novel compound 5-oxo-l-cyclopentene-l-heptanoic acid (AY-16, 804) was determined.The effects on platelet aggregation of the known inhibitors were consistent with information in the literature. Prostaglandin E1 was the most potent inhibitor in both techniques; sulfinpyrazone inhibited aggregation in both models but was less potent than prostaglandin E1. AY-16, 804 exhibited activity in vitro and in vivo similar to that of sulfinpyrazone. Dipyridamole did not inhibit platelet aggregation in vivo and did not inhibit aggregation in vitro in concentrations at which it remained soluble.The filter loop technique is a suitable model for measuring platelet aggregation in the flowing blood of the rat. It is a relatively simple method of determining aggregation and easily adapted to other species.


1987 ◽  
Vol 5 (2) ◽  
pp. 292-298 ◽  
Author(s):  
R P Warrell ◽  
N W Alcock ◽  
R S Bockman

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.


Sensors ◽  
2021 ◽  
Vol 21 (15) ◽  
pp. 5040
Author(s):  
Silvia Ronda Peñacoba ◽  
Mar Fernández Gutiérrez ◽  
Julio San Román del Barrio ◽  
Francisco Montero de Espinosa

Despite the use of therapeutic ultrasound in the treatment of soft tissue pathologies, there remains some controversy regarding its efficacy. In order to develop new treatment protocols, it is a common practice to carry out in vitro studies in cell cultures before conducting animal tests. The lack of reproducibility of the experimental results observed in the literature concerning in vitro experiments motivated us to establish a methodology for characterizing the acoustic field in culture plate wells. In this work, such acoustic fields are fully characterized in a real experimental configuration, with the transducer being placed in contact with the surface of a standard 12-well culture plate. To study the non-thermal effects of ultrasound on fibroblasts, two different treatment protocols are proposed: long pulse (200 cycles) signals, which give rise to a standing wave in the well with the presence of cavitation (ISPTP max = 19.25 W/cm2), and a short pulse (five cycles) of high acoustic pressure, which produces a number of echoes in the cavity (ISPTP = 33.1 W/cm2, with Pmax = 1.01 MPa). The influence of the acoustic intensity, the number of pulses, and the pulse repetition frequency was studied. We further analyzed the correlation of these acoustic parameters with cell viability, population, occupied surface, and cell morphology. Lytic effects when cavitation was present, as well as mechanotransduction reactions, were observed.


Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1224-1231 ◽  
Author(s):  
Ursula B. Kaiser ◽  
Andrzej Jakubowiak ◽  
Anna Steinberger ◽  
William W. Chin

Abstract The hypothalamic hormone, GnRH, is released and transported to the anterior pituitary in a pulsatile manner, where it binds to specific high-affinity receptors and regulates gonadotropin biosynthesis and secretion. The frequency of GnRH pulses changes under various physiological conditions, and varying GnRH pulse frequencies have been shown to regulate differentially the secretion of LH and FSH and the expression of the gonadotropin α, LHβ, and FSHβ subunit genes in vivo. We demonstrate differential effects of varying GnRH pulse frequency in vitro in superfused primary monolayer cultures of rat pituitary cells. Cells were treated with 10 nm GnRH pulses for 24 h at a frequency of every 0.5, 1, 2, or 4 h. α, LHβ, and FSHβ messenger RNA (mRNA) levels were increased by GnRH at all pulse frequencies. α and LHβ mRNA levels and LH secretion were stimulated to the greatest extent at a GnRH pulse frequency of every 30 min, whereas FSHβ mRNA levels and FSH secretion were stimulated maximally at a lower GnRH pulse frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were increased by GnRH at all pulse frequencies and were stimulated maximally at a GnRH pulse frequency of every 30 min. Similar results were obtained when the dose of each pulse of GnRH was adjusted to maintain a constant total cumulative dose of GnRH over 24 h. These data show that gonadotropin subunit gene expression is regulated differentially by varying GnRH pulse frequencies in vitro, suggesting that the differential effects of varying GnRH pulse frequencies on gonadotropin subunit gene expression occur directly at the level of the pituitary. The pattern of regulation of GnRHR mRNA levels correlated with that of α and LHβ but was different from that of FSHβ. This suggests that α and LHβ mRNA levels are maximally stimulated when GnRHR levels are relatively high, whereas FSHβ mRNA levels are maximally stimulated at lower levels of GnRHR expression, and that the mechanism for differential regulation of the gonadotropins by varying pulse frequencies of GnRH may involve levels of GnRHR. Furthermore, these data suggest that the mechanisms whereby varying GnRH pulse frequencies stimulate α, LHβ, and GnRHR gene expression are similar, whereas the stimulation of FSHβ mRNA levels may be different.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Junjie Niu ◽  
Weimin Sang ◽  
Feng Zhou ◽  
Dong Li

Purpose This paper aims to investigate the anti-icing performance of the nanosecond dielectric barrier discharge (NSDBD) plasma actuator. Design/methodology/approach With the Lagrangian approach and the Messinger model, two different ice shapes known as rime and glaze icing are predicted. The air heating in the boundary layer over a flat plate has been simulated using a phenomenological model of the NSDBD plasma. The NSDBD plasma actuators are planted in the leading edge anti-icing area of NACA0012 airfoil. Combining the unsteady Reynolds-averaged Navier–Stokes equations and the phenomenological model, the flow field around the airfoil is simulated and the effects of the peak voltage, the pulse repetition frequency and the direction arrangement of the NSDBD on anti-icing performance are numerically investigated, respectively. Findings The agreement between the numerical results and the experimental data indicates that the present method is accurate. The results show that there is hot air covering the anti-icing area. The increase of the peak voltage and pulse frequency improves the anti-icing performance, and the direction arrangement of NSDBD also influences the anti-icing performance. Originality/value A numerical strategy is developed combining the icing algorithm with the phenomenological model. The effects of three parameters of NSDBD on anti-icing performance are discussed. The predicted results show that the anti-icing method is effective and may be helpful for the design of the anti-icing system of the unmanned aerial vehicle.


Author(s):  
Leoni Villano Bonamin ◽  
Thaís Cristina Silva ◽  
William Alves Santos ◽  
Sandra AG Pinto ◽  
Vanessa Xavier ◽  
...  

Background: There are few published researches about the exclusive use of Carsinosinum in several potencies to treat cancer. The name Carcinosinum refers to any homeopathic preparation of epithelial cancerous tissues and is especially indicated when there are any hereditary and familial antecedents of cancer, tuberculosis, diabetes, pernicious anemia or a combination of two or more of these diseases. Homeopathic complexes which include Conium Maculatum, Sabal Serrulata, Thuja Occidentalis and Carcinosinum can reduce in 23% the incidence of prostate cancer in vivo and in 38% the tumor volume, compared to untreated groups. Another in vivo study revealed reduction of symptoms and increase of survival time in mice bearing Ehrlich ascitic carcinoma, after treatment with Carcinosinum 200cH. In vitro, Carcinosinum 200cH can increase the expression of the pro-apoptotic gene p53. However, mice treated with Carcinosinum 6cH had the highest percentage and diversity of symptoms compared to other treatments, which demonstrate the importance of homeopathic potency in pro or anti-carcinogenic action. Considering that the literature on this subject is still rare and focused on genotypic and clinical effects, the present study was proposed, with the aim of identifying the possible phenotypic changes, including viability, HER-2 expression and metastatic skills, using 4T1 cells in vitro as a model, after treatment with Carcinosinum in different homeopathic working dilutions (12cH; 30cH; 200cH), prepared mechanically (Denise Machine, Autic®) in our laboratory using sterile pure water, from a commercial matrix (HN Cristiano, São Paulo, Brazil) stocked in 70% hydro-alcoholic solution. The final dilutions were inserted in the culture medium in a volume equal to 10%, at the time of cell seeding. The same succussioned vehicle used to prepare the medicines (70% hydro-alcoholic solution), from the same batch and diluted 1:100 in sterile pure water, was used as control. All treated cells were cultivated in bottles of 25ml with cell density of 5 x 105 cells / ml and, after 24 hours of treatment, they were analyzed for the apoptosis index using the Annexin V kit and measured by the Countess® system. The morphology of the 4T1 cells was monitored by staining fixed cell smears with hematoxylin-eosin method. The samples were evaluated in quadruplicate and the data were analyzed by one-way ANOVA. The results obtained up to now show that the treatment with Carcinosinum 12cH produced a different pattern of cell death compared to the other treatments, with significant reduction in apoptosis index (one-way ANOVA, p=0.01) and clear hydropic degeneration phenotypic pattern. The analysis of HER-2 expression and metastatic skill will be the next step of this research.


Blood ◽  
1982 ◽  
Vol 60 (4) ◽  
pp. 814-821 ◽  
Author(s):  
S Ladisch ◽  
W Ho ◽  
D Matheson ◽  
R Pilkington ◽  
G Hartman

Depressed cellular immune function and increased susceptibility to infection characterize familial erythrophagocytic lymphohistiocytosis (FEL), a usually fatal autosomal recessive disease. One component of the immunodeficiency is plasma-mediated inhibition of lymphocyte proliferation. We have tested whether repeated plasma or blood exchange would decrease plasma inhibitory activity and improve cellular immune function in FEL. Following this treatment, reduction in plasma inhibitory activity, reversal of depressed antigen-specific lymphocyte proliferative responses and monocyte antibody-dependent cytotoxic function in vitro, and clinical improvement were complete in two and partial in one of three patients studied. Relapse, which was ultimately fatal, was associated with recurrence of the immune defects. These findings suggest that cellular immunodeficiency in FEL is acquired and possibly related to circulating immunosuppressive activity, the removal of which is associated with transient immunologic and clinical recovery.


2021 ◽  
Vol 12 ◽  
Author(s):  
M G Vossen ◽  
S Pferschy ◽  
C Milacek ◽  
M Haidinger ◽  
Mario Karolyi ◽  
...  

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.


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