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Biomedical subjects

D Cathignol

Publications and source records attributed to D Cathignol.

At least 19 recordsLinked to original sources

[Tumor ablation with focalized ultrasound. In vivo experiment with prostatic adenocarcinoma R3327 Mat-Ly-Lu].

Ultrasound can induce tissue lesions by a combination of thermal and mechanical effects related to the tissue absorption of the energy emitted at the focal point of the transducer. The effects of focused ultrasound were studied in vivo in Fisher/Copenhagen hybrid rats bearing Dunning R3327 experimental prostatic carcinoma. The experimental tumour was transplanted by subcutaneous injection into the abdomen of 20 mg of tumour tissue derived from the Mat-Ly-Lu strain. Treatment was performed under general anaesthesia. The animal, maintained in a sarcophage exposing the tumour, was immersed in degassed water ensuring the interface between the tumour and the 1 MHz transducer. The displacements of the transducer were guided by computerised ultrasound screening, allowing irradiation of the entire tumour. The energy was supplied by a 7.5 kW amplifier in the form of series of impulses of variable duration. 77 rats were treated and the tumour growth was compared to that of non-irradiated control rats. Comparative series demonstrated the following results: 1. Immediate tumour destruction was obtained with a very high acoustic intensity (9,000 Watts/cm2) and a brief exposure time. 2. A transient slowing of the tumour growth rate was observed for an acoustic intensity of between 3,500 and 5,500 Watts/cm2. 3. Partial or total necrosis of the tumour was obtained with intensities of between 300 and 2,750 Watts/cm2 and a long exposure time. Total tumour destruction was obtained in 30 of the 49 rats treated under these conditions. 14 animals developed a local recurrence, 9 animals did not develop a local recurrence but developed metastases and 7 animals obtained long-term survival without local recurrence or metastasis. Under certain experimental conditions, focused ultrasound, without any adjuvant treatment, was able to destroy the Dunning R3327 Mat-Ly-Lu strain experimental tumour and, in certain cases, induced complete cure of this experimental cancer.

Animals

[Transesophageal echo-Doppler in children: the importance of the exact measurement of the aortic diameter and its variations over time for estimating the aortic output].

The purpose of the study was to evaluate a new non invasive system of hemodynamic monitoring. The aortic systolic, diastolic and mean diameter have been measured with eco-TM and the aortic blood flow with pulsed Doppler, in order to obtain the aortic output. The aortic systolic diameter and the derived aortic output were then compared to the corresponding values obtained with CT. Ten healthy children were asked to be explored with CT under general anaesthesia and an oesophageal probe was positioned. The mean aortic diameter value was 7.18 +/- 0.91 mm. The systolic and diastolic aortic diameter was 7.87 +/- 0.91 mm and 6.65 +/- 1 mm respectively. The aortic systolic diameter measured with CT was 8.2 +/- 0.92 mm. Correlation analysis with aortic systolic diameter with eco TM as the dependent variable and aortic systolic diameter with CT as the independent variable revealed a highly significant correlation (r = 0.95, coefficient of determination 0.90). The mean percentage difference between systolic and diastolic diameter measured with TM eco scan was 15% with maximum variation 22% and minimum of 10% (p less than 0.003). The aortic blood flow calculated from the systolic aortic diameter was 29% higher than that obtained from diastolic aortic diameter. This would suggest that the correct measurement of the aortic diameter has to be considered in the final evaluation of aortic output especially in children in whom the elasticity of the aortic wall represents a major factor in determining fluctuations of aortic diameter.

Aorta

Cytotoxic effects of acoustic cavitation on HT-29 cells and a rat peritoneal carcinomatosis in vitro.

Damage to cells and tissues exposed to shock waves (SWs) is thought to be secondary to cavitation phenomena involving the collapse of gas bubbles in a fluid. Using HT-29 cells and DHDK12PROb tumors, we tried to enhance SW-related damage by the simultaneous administration of gas microbubbles. Bubbles resulted from a mixture of air and gelatin (HT-29 cells) or from a carbonated NaCl solution (tumors). HT-29 cells in suspension received either SW (50, 250, or 1000 SWs) alone or in association with bubbles. Trypan blue-negative cells decreased as the number of SWs increased. Exposure to SWs and bubbles resulted in not only an increased but also a delayed mortality as compared to SWs only. One thousand SWs with bubbles induced a complete inhibition of cell growth, with cytoplasmic vacuolae, ruptured membranes, and abnormal nuclear shape and chromatin. Exponential and confluent cells exhibited a similar mortality and growth. DHDK12PROb tumors received either SWs only (50, 100, 250, 500, or 1000 SWs) or SWs with bubbles in vitro. Thymidine incorporation was significantly lower after exposure to SWs with bubbles as compared with controls and SWs only; it was nil by 1000 SWs with bubbles. Histopathological features of tumors exposed to SWs with bubbles included erosion and hemorrhage, disorganized structure, pyknotic nuclei, and cytoplasmic vacuolae. We conclude that cavitation, as produced by a combination of SWs and gas microbubbles, can achieve bioeffects which are relevant to cancer therapy.

Animals

Physicochemical determinants of in vitro shock-wave biliary lithotripsy.

Human gallstones were studied by visual inspection, computerized tomographic imaging, and chemical analysis to assess physicochemical characteristics that may determine the outcome of in vitro shock-wave fragmentation. Eighty-five stones (mean diameter: 13.2 +/- 5 mm) were each collected from different patients. Fifty-five (65%) calculi were angular and 30 (35%) round or oval-shaped. Three easily obtained measures were derived from each stone's optimal computerized tomographic image including the mean stone density, a measure corresponding to the standard deviation of the mean stone density value which we termed the stone density distribution index and which may reflect the physicochemical heterogeneity of a given gallstone, as well as the density range. After the administration of 2500 shock waves using an electrohydraulic generator, fragmentation was noted in 68 calculi (80%) and was satisfactory in 27 (32%) (where the largest resulting fragment diameters were all less than or equal to 5 mm). Strong determinants of satisfactory fragmentation on multivariate analysis included a stone diameter of less than or equal to 15 mm, the presence of an angular stone shape, and a stone density distribution index of greater than or equal to 60 Hounsfield units. The other parameters did not independently determine satisfactory fragmentation. Prospective clinical trials are needed to assess whether these findings result in a better prediction of the success of extracorporeal biliary lithotripsy and a broadening of its indications.

Chemical Phenomena

Volume measurement by ultrasonic transverse or sagittal cross-sectional scanning.

A technique is described that provides an accurate estimation of the volume of an organ from its ultrasonic cross-sectional images. The technique is applied to two types of ultrasonic investigation, one providing transverse and the other sagittal images. The organ outline has to be traced on each scan. The computer first calculates the area and then the volume from the vector areas and the centroids of a series of sections. The technique has been tested with phantoms of various shapes and volumes made with agar gel. These experiments show that the error in the volume estimation is less than 10% and the variability of measurements is less than 2%.

Acoustics

Assessment of a potentially noninvasive method for monitoring aortic blood flow in children.

Ultrasonic methods have rendered possible noninvasive quantitative blood flow measurement. In this work, a method is proposed to measure aortic blood flow in children by means of a specially designed miniaturized esophageal probe and an autonomous apparatus combining an M-mode imaging system and a pulsed Doppler. In vivo experimental results in animals are presented and demonstrate the interest of simultaneous and continuous measurement of aortic diameter and blood flow velocity giving accurate measurements. A 0.94 correlation coefficient is found when comparing blood flow in the descending aorta measured using this method and using an electromagnetic flowmeter.

Animals

Influence of water conductivity on the efficiency and the reproducibility of electrohydraulic shock wave generation.

In an electrohydraulic generator, two underwater metal electrodes are connected with a capacitor charged to a high voltage. When the circuit is switched on, a plasma is generated reaching temperatures of thousands of K, resulting in a compressive pressure pulse. The formation of the plasma is a nonreproducible phenomenon inducing great variations of the pressure pulse. When the electrodes are immersed in an electrolyte instead of degassed water, the conditions of electrical discharge are dramatically modified. The latency time and the amplitude of the oscillations of the discharge current decrease as the conductivity of the electrolyte increases. For a conductivity of 7 omega.cm, there is no latency, and the critically damped discharge is achieved. The expanding pressure wave is increased by 10%, and the mean peak pressure value over 120 shocks at the second focus after focalization is increased by 50%. The relative standard deviation of the pressure value at the second focus is only 5%, while it is about 30% in ordinary water. The fragmentation efficiency is considerably increased because total fragmentation is obtained in 220 shocks instead of 450 shocks in ordinary water when standard stones are used, and in 131 shocks instead of 304 shocks when gallstones are used. Last, we show that the wear of the electrodes is reduced by a factor 8 when electrolyte is used. The improvement is supposed to have two causes: First, the energy is delivered into the medium in a shorter time, and, second, the center of the shock wave is always located at the same place. The decreased wear should make it possible to treat a much greater number of patients without changing electrodes, and the enhancement of the pressure should increase the efficiency of the fragmentation of the gallstones without aggravating the patient's pain.

Efficiency

[Tissue ablation by focused ultrasound].

Tissue lesions can be induced at the focal point of highly focused transducers with a frequency of 1 and 2.25 MHz for exposure times of less than 1 second. The energy generated by a high power amplifier (7.5 kilowatts effective at 1 MHz) is delivered in the form of series of impulses lasting between 10 and 1,000 milliseconds. The experimentation was conducted in the rat kidney (the left kidney, normally supplied by its vascular pedicle, was exteriorised during ultrasound treatment and then returned to the abdomen). The animal was sacrificed 3 days later and the lesions were studied by serial histological sections. 248 ultrasound shots were performed between January and September 1990. They allowed the definition of the time and intensity constants necessary to induce total destruction of the renal tissue at the focal point. Depending on the energy delivered, an elliptical cavity with a mean height of 1.2 to 4.6 mm and a mean diameter of 0.6 to 3 mm is observed at the focal point after a single shot. No cell structures were visible in the cavities and, in general, the cavity was prolonged by a cone-shaped region of coagulated necrosis with an inferior base. The mechanism responsible for this focused ultrasonic tissue destruction (FUTD) involves a variable combination of thermal and mechanical effects which depends on the ultrasound intensity delivered at the focal point of the transducer.

Amplifiers, Electronic

Hepatic lesions in the rabbit induced by acoustic cavitation.

Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma.

Animals

A novel method to control P+/P- ratio of the shock wave pulses used in the extracorporeal piezoelectric lithotripsy (EPL).

There is growing evidence that acoustic cavitation plays an important role in stone fragmentation during extracorporeal shock wave lithotripsy (ESL) treatment. In addition, side effects of the treatment, such as the hemorrhage and destruction of the tissue in the vicinity of the stone are also ascribed to cavitation phenomenon. Since cavitation is associated with the maximum negative pressure in the shock pulse, it would thus appear that possibility of controlling this pressure would be desirable in ESL applications. This paper describes a novel technique developed to control the ratio of compressional peak (P+) to rarefactional peak pressure (P-) of the shock wave for use in lithotripsy treatment. The procedure is based on the finite amplitude wave generation by focused piezoelectric transducers and subsequent interaction of the shocked waves in the common focal region. The highly asymmetrical shock wave is produced in the focal region by providing an appropriate time delay to each of the high voltage electrical excitation signals which drive the transducers. The degree of relative reduction of negative halfcycles and the corresponding positive halfcycles amplification increases with the number of the acoustic sources used. The practical implementation of the shock wave generator was obtained by using 5 cm diameter, focused 1 MHz transmitter, and additional transducers of identical construction having frequencies corresponding to the harmonics and subharmonics of the 1 MHz frequency. The importance of the results for the future development of lithotripters, and stone treatment efficiency is pointed out.

Acoustics

Inhibition of coronary artery thrombosis by SIN-1, a donor of nitric oxide.

Molsidomine and its metabolite, SIN-1, a donor of nitric oxide, are potent coronary vasodilator and anti-ischemic agents. Recently, SIN-1 and nitric oxide have also been shown to inhibit platelet adhesion and aggregation in vitro. The present study in dogs was designed to evaluate the in vivo antithrombotic properties of SIN-1. Coronary intimal damage and stenosis are known to induce coronary cyclic flow variations that reflect platelet thrombus formation followed by disaggregation and embolization (Folts preparation). This model of coronary artery thrombosis appears to simulate the combination of some of the factors contributing to unstable angina and myocardial infarction in human. SIN-1 infusion (10 micrograms/kg/min) significantly reduced the frequency of cyclic flow variations: 4.9 +/- 6.2/h vs. 14 +/- 4.6/h (before treatment, p less than 0.03, n = 6). Results were similar to those obtained with aspirin (5 mg/kg, bolus i.v.: 1.5 +/- 0.6/h vs. 11.7 +/- 3/h, p less than 0.03, n = 5) whereas saline had no effect (17.8 +/- 2.2/h vs. 19.3 +/- 2.4/h, n = 5). As expected, blood pressure was decreased only in the SIN-1 group: 56.2 +/- 7.8 vs. 87.3 +/- 9.3 mm Hg (p less than 0.02) (mean arterial blood pressure). The present results suggest that the well-documented anti-ischemic properties of SIN-1 could be partly due to its antithrombotic activity, clearly demonstrated with the model of coronary thrombosis used here in the dog.

Animals

[Noninvasive hemodynamic monitoring via the integration of data obtained by ECG, aortic flow by Doppler esophageal probe and by finger plethysmography].

The aims of this work are to describe the general and technical characteristics of a new device for the noninvasive monitoring of patients in intensive care and during general anaesthesia, and the results concerning the reliability of this method. An ultrasonic esophageal probe and an echo-Doppler device have been used to obtain continuous data of the aortic diameter and of blood velocity. Aortic output is calculated automatically. This method, together with other non-invasive monitoring techniques (blood pressure, heart rate, rhythm and cardiac conduction), gives on the one hand the data of aortic output, systemic peripheral resistance and stroke volume; on the other, through a computerized elaboration, the systolic time intervals (PEP pre-ejection period, LVET left ventricular ejection time, QS2 electromechanical systole, PEP/LVET ratio of PEP to LVET). The validation of STI data, has been obtained through 125 comparative measurements for each of the three parameters. The data obtained through the aortic velocity waveform in descending aorta (pulsed Doppler) have been compared with those obtained through the aortic pressure waveform (intra aortic catheter). The correlation was: PEP 0.92, LVET 0.95, QS2 0.93. The clinical application of this method supplies data concerning cardiac load, after-load and indirectly cardiac pre-load. This non-invasive procedure gives us a continuous measurement of hemo-dynamic situation, which allows the physician to plan and evaluate the therapeutical efficacy. Finally new pathologic events may be opportunely faced.

Anesthesia, General

[Non-invasive monitoring of hemodynamic profile during general anesthesia].

This article presents a general vision of a new non-invasive cardiovascular monitoring technique applied to patients during general anaesthesia. This method employs an esophageal eco-Doppler, able to supply a continuous measurement of the aortic diameter (eco-TM) and of the velocity of aortic blood flow (pulsed Doppler) for the calculation of aortic output; a monitor to survey the ECG and a noninvasive device for the measurement of blood pressure. The resulting data, opportunely processed by the computer, supply the values of aortic output, of systemic peripheral resistances and of stroke volume. The last two parameters are indexed with aortic output. Through the computer analysis of ECG and of the aortic velocity curve, it is possible to trace back the systolic time intervals and find out the left ventricular ejection time, the pre-ejection period and the electromechanical systole. All these values are indexed with heart rate. The validation of this method gave good results. The comparison between aortic output, measured by the eco-Doppler, and the value obtained with the thermodilution gave a correlation of r = 0.97, and comparing it with the one obtained with the electromagnetic ring, the correlation was r = 0.96. The aortic diameter was calculated with computerized tomography and the correlation between the two diameters resulted in 0.978. This method is quite useful because it supplies continuous parameters in an automatic and noninvasive way. Therefore it is possible, through a compete hemodynamic profile, to diagnose the variations and control the evolutions of the hemodynamic profile induced by the therapeutical treatments, on the basis of a correct physiopathological interpretation.

Anesthesia, General

Comparison of the diagnostic value of sonography and rectal examination in cancer of the prostate.

The value of endorectal sonography for the diagnosis of prostatic cancer was established after retrospective interpretation of sonographic findings in 213 patients, without prior knowledge of either the clinical or pathological data. Endorectal sonography was performed by the authors with a mechanical sectorial high frequency (7.5 MHz) probe. A pathology report (73 biopsies, 52 TUR, 7 suprapubic adenomectomy specimens) was available from 132 patients: 25 pathological examinations were interpreted as normal; 41 adenomas; 24 prostatitis or fibrosis, and 42 cancers (5 clinical stage T0, 22 T1, 2 T2 and 13 T3). Specificity for the diagnosis of cancer was 65 or 81%, respectively, according to the normality reference considered, i.e. either the group of patients having a normal pathological control (90 patients) or the same group plus another group of patients with a normal rectal examination (171 patients). The sensitivity for the diagnosis of cancer was only 48%. 43% of cancers were falsely interpreted as prostatitis or adenomas and 9% as normal (2 T0 and 2 T1). The large proportion of local stages without capsular involvement (29 of 42) is partly responsible for this lack of sensitivity. Rectal examination and sonography are complementary techniques. In the same study, rectal examination had a 48% specificity and a 92% sensitivity.

Adenoma

Thromboresistance of bulk heparinized catheters in human.

Bulk heparinized catheters (1 mm internal diameter) containing 10% heparin ionically bound, were tested in four human volunteers. Catheters containing 0% and 10% heparin were compared in each individual using ultrasound microflow velocimetry, permeability test, sequential determinations of activated partial thromboplastin time, heparin levels and generation of Fibrinopeptide A, beta thromboglobulin and Platelet factor 4. Although the release of heparin expressed by its anti-IIa activity is of similar range in the four individuals the release of anti-Xa activity is variable and generally of greater magnitude, suggesting a privileged migration of low molecular weight components of heparin. These antiproteasic activities of heparin are sufficient to inhibit fibrin formation and blood coagulation despite their relative inability to prevent platelet activation.

Catheters, Indwelling

Evaluation of bladder cancer with a miniature high frequency transurethral ultrasonography probe.

A miniature high frequency 10 MHz transurethral ultrasonography probe has been developed which is adaptable to any standard 17 F cystoscope sheath. High frequency contributed to a definite improvement in image resolution but did not allow distinct visualisation of different bladder wall layers. An 80% correlation between ultrasonographic and pathological staging was established after evaluation of 50 consecutive patients with newly diagnosed bladder tumours. Ta/T1 tumours tended to be overstaged with ultrasound. In some patients, the response to conservative treatment (external beam radiation therapy) of deeply infiltrating tumours could be assessed with the miniature probe on an out-patient basis.

Cystoscopy