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PubMed1991

The disposition of [14C]-labelled benazepril HCl in normal adult volunteers after single and repeated oral dose.

1. The disposition of [14C]-labelled benazepril HCl, an ACE-inhibitor, was studied in four normal adult volunteers after a single oral dose of 20 mg and after repeated doses of 20 mg once daily for 5 days. Radioactivity was measured in plasma, urine and faeces. The prodrug ester benazepril and the pharmacologically active metabolite benazeprilat were determined quantitatively in plasma and urine by a g.c.-m.s. method. The pattern of metabolites in urine was analysed semiquantitatively by h.p.l.c.-radiometry. 2. After a single oral dose at least 37% was absorbed, as indicated by urinary recovery. The peak plasma concentration of benazepril (0.58 +/- 0.13 nmol/g (SD] was observed at 0.5h after dose, indicating rapid absorption. Peak concentrations of radioactivity (1.88 +/- 0.48 nmol/g) and of active benazeprilat (0.84 +/- 0.25 nmol/g) were observed at 1 h after dose, demonstrating rapid bioactivation. 3. The area under the plasma curve (AUC0-96 h) of total radioactivity amounted to 9.7 +/- 1.1 (nmol/g)h, 5% of which was accounted for by benazepril and about 50% by benazeprilat. 4. Over 9 days 96.8 +/- 0.5% of the dose was excreted in urine and faeces. Urinary excretion accounted for 37.0 +/- 6.0% of the dose, 80% of which was recovered in the first 8 h after dosing. 5. In urine, only 0.4% of the dose (1% of the radioactivity) was excreted as unchanged benazepril, indicating that the compound was extensively metabolized. Benazeprilat accounted for 17% of the dose (about half of the radioactivity; 0-96 h). Glucuronide conjugates of benazepril and benazeprilat constituting approximately 11% and 22% of the radioactivity (about 4% and 8% of the dose; 0-48 h) were tentatively identified. 6. Repeated oral treatment with benazepril HCl did not influence the pharmacologically relevant kinetics and disposition parameters.

Administration, Oral↗
PubMed1992

Linoleate-dependent co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by rat cytosolic lipoxygenase.

1. Co-oxygenation of 14C-labelled benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol was studied in rat lung cytosol, using linoleic acid as a co-substrate. Covalently bound and soluble metabolites were quantified by radiometry and h.p.l.c., respectively. 2. The co-oxygenation resulted in the production of reactive metabolites capable of protein binding as well as a series of soluble derivatives. 3. Co-oxygenation of benzo(a)pyrene yielded primarily a significant amount of benzo(a)pyrene-6,12-dione while benzo(a)pyrene-7,8-dihydrodiol led to a significant amount of benzo(a)pyrene-trans-anti-tetrol. 4. Their production was abolished by addition of 25 microM of the lipoxygenase inhibitor and antioxidant NDGA. 5. It is postulated that the linoleic acid peroxyl radicals, formed by rat lung lipoxygenase, initiate the one-electron oxidation of benzo(a)pyrene to its quinones, and epoxidation of benzo(a)pyrene-7,8-diol to the ultimate carcinogenic benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide.

Animals↗
PubMedDate not supplied

The influence of tissue layering on microwave thermographic measurements.

Non-invasive thermal imaging and temperature measurement by microwave radiometry has been investigated for medical diagnostic applications and monitoring hyperthermia treatment of cancer, in the context of heterogeneous body structure. The temperature measured by a radiometer is a function of the emission and propagation of microwaves in tissue and the receiving characteristics of the radiometric probe. Propagation of microwaves in lossy media was analysed by a spectral diffraction approach. Extension of this technique via a cascade transmission line model provides an efficient algorithm for predicting the field patterns of aperture antennas contacting multi-layered tissue. A coherent radiative transfer analysis was used to relate the field pattern of a radiating antenna to its receiving characteristics when used as a radiometer probe, leading to a method for simulating radiometric data. Measurements and simulations were used to assess the effect of overlying fat layers upon radiometer response to temperature hot spots in muscle-type media. Results suggest that dielectric layering in tissue greatly influences measured temperatures and should be accounted for in the interpretation of radiometric data.

Fats↗
PubMedDate not supplied

Experimental thermoradiotherapy of human tumour xenografts in nude mice; design of the hyperthermia system.

An experimental thermoradiotherapy study was started in 1986. For this study a hyperthermia system was developed for heating human tumours xenotransplanted into nude mice. The treatment device was a four-channel computer-controlled hyperthermia system. Temperature was monitored by microwave radiometry at 3 GHz. Specifications of the radiometer were evaluated first under reference conditions. Subsequently, thermal dosimetry was studied using non-invasive measurement of brightness temperature, TOR. Hyperthermia treatments were simulated in phantom material with radiometric monitor values, TR, of 40 and 41. In conjunction with the parameters of TOR, surface temperature, T0, and water bolus temperature, TW, thermal modelling was performed. Influence of a perfused phantom also was studied on microwave thermometry.

Animals↗
PubMedDate not supplied

915 MHz microwave interstitial hyperthermia. Part III: Phase II clinical results.

From October 1989 to October 1991, 16 patients (17 tumours) with locally advanced carcinomas of the oral tongue and eight patients with second carcinomas of the base of tongue in previously irradiated areas, have been treated by means of an interstitial hyperthermia-brachytherapy combination in a phase II clinical trial. Each miniature microwave antenna of our hyperthermia system, called HIMCAR, is used both for heating and for thermal measurements by microwave radiometry at 3 and 9 GHz (see Part I). Among these 25 lesions (21 T2, 4 T3), 21 showed a complete response (15/17 locally advanced carcinomas and 6/8 second carcinomas in previously irradiated areas). The toxicity was not severe (less than 10%). A French multicentre phase III study is now under way.

Body Temperature↗
PubMed1998

Chimeric antibodies with specificity for tumor antigens: demonstration of in situ localization to tumors after antibody therapy.

In this study, we compare various methods for the detection of a tumor-associated target antigen and deposition of the bound therapeutic monoclonal antibody in patients enrolled in two separate trials, one involving the administration of two radiolabeled monoclonal antibodies and the other involving an unlabeled antibody. In the first trial, patients with TAG-72 expressing metastatic colon cancer scheduled for surgical intervention received radiolabeled murine and chimeric B72.3 antibody followed by radioimmune imaging and subsequent laparotomy. Normal and tumor tissues obtained at surgery were processed for routine histology, immunohistochemistry, radiometry, and autoradiography. Both anti-TAG-72 antibodies localized to known tumor sites as evidenced by radioimmune imaging. Resected tissue revealed a high tumor-to-normal radiolocalization ratio, and autoradiography demonstrated even deposition of the radiolabeled antibodies throughout the entire tumor deposit with sparing of surrounding normal tissue. In contrast, immunohistochemistry on the same sections revealed comparatively weak antigen expression and patchy antibody localization. In the second trial, patients with GD2 antigen expressing metastatic melanoma received the unlabeled chimeric anti-GD2 antibody C14.18. Immunologic detection of the GD2 antigen and C14.18 deposition was performed on biopsy section as well as on single cell suspension. FACS analysis of the single cell suspension proved more sensitive for the detection of bound antibody than immunohistochemistry, although both methods yielded comparable results for GD2 antigen expression. Our findings demonstrate that the optimal method for the detection of tumor-associated antigen and bound therapeutic antibody can vary depending upon the nature of the antibody (radiolabeled vs. unlabeled and murine vs. chimeric), fixation stability of the target antigen, and the type of pathologic material available for study.

Animals↗
PubMed2006

Primary pancreatic lymphoma: report of six cases.

AIM: To heighten recognition of primary pancreatic lymphoma (PPL) in clinical practice. METHODS: A retrospective review of the clinical presentation, imaging characteristics and pathological features of PPL patients were presented, as well as their diagnosis and treatment, in combination with literature review. RESULTS: Histological diagnosis was made in four patients by surgery and in two patients by EUS-FNA. The six PPL patients (5 males and 1 female; age range, 16-65 years; mean age, 46 years) had the duration of symptoms for two weeks to three months. The primary presenting symptoms, though not characteristic, were abdominal pain, abdominal masses, weight loss, jaundice, nausea and vomiting. One of the patients developed acute pancreatitis. In one patient, the level of serum CA19-9 was 76.3 microg/L. Abdominal CT scan showed that three of the six tumors were located in the head of pancreas, two in the body and tail, and one throughout the pancreas. Diameter of the tumors in the pancreas in four cases was more than 6 cm, with homogeneous density and unclear borders. Enhanced CT scan showed that only the tumor edges were slightly enhanced. The pancreatic duct was irregularly narrowed in two cases whose tumors were located in the pancreatic head and body, in which endoscopic retrograde cholangiopancreatography (ERCP) showed that the proximal segment was slightly dilated. Two patients underwent Whipple operation, one patient underwent pancreatectomy, and another patient underwent operative biliary decompression. PPL was in stage I E in 2 patients and in stage II E in 4 patients according to the Ann Arbor classification system. The diagnosis of B-cell non-Hodgkin's lymphoma was made in all patients histopathologically. All six patients underwent systemic chemotherapy, one of whom was also treated with gamma radiometry. One patient died two weeks after diagnosis, two patients lost follow-up, two patients who received chemotherapy survived 49 and 37 mo, and the remaining patient is still alive 21 mo, after diagnosis and treatment. CONCLUSION: PPL is a rare form of extranodal lymphoma originating from the pancreatic parenchyma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, which deserves attention. EUS-guided fine-needle aspiration (EUS-FNA) of the pancreas requires experienced cytopathologists as well as advanced immunohistochemical assays to obtain a final diagnosis on a small amount of tissue. Surgery and adjuvant chemotherapy or radiotherapy can produce fairly good outcomes.

Adolescent↗
PubMed1984

Distribution of suprofen in rats of both sexes.

The tissue distribution of 3H-labeled DL-2-(4-(2-thienylcarbonyl) phenyl) propionic acid (suprofen) after po administration was studied in male, female, and pregnant rats by radiometry. The only tissues with concentrations comparable to plasma levels were those involved in metabolism and excretion (liver and kidney), except for the gastrointestinal tract, and all other tissue levels were very low. In pregnant rats, radioactivity crossed the blood-placenta barrier to a moderate extent and low concentrations were found in fetuses. Radioactivity disappeared from most tissues of male, female, and pregnant rats at rates similar to that from plasma and no appreciable radioactivity was found in rat tissues 24 h after dosing.

Administration, Oral↗
PubMed1994

[Transurethral microwave thermotherapy for benign prostatic hyperplasia: a 1-year follow-up study].

The authors studied a 1-year effect of transurethral microwave thermotherapy (TUMT) using the PROSTCARE apparatus (Bruker Spectrospin Wissembourg, Frace) on 35 patients with symptomatic benign prostatic hyperplasia (BPH). The device is equipped with a unique non-invasive system "radiometry" for the measurement of the intraprostatic temperature to regulate the microwave emission power and to eliminate classic surface controls. All of the 35 patients received a single thermotherapy session (60 minutes), the average intraprostatic temperature was 43.6 +/- 1.2 degrees C (mean +/- SD) and the average power output was 43.9 +/- 4.1 Watt. The clinical effects were evaluated at 2 months, 6 months and 1 year after TUMT by a specially designed score scale for subjective symptoms and objective findings as compared with the pretreatment score. Assuming that more than a 25% reduction of the total score indicates "effective", 71.4%, 71.4, and 48.6% of the treatments remained effective at 2 months, 6 months, and 1 year after TUMT, respectively. The maximum prostatic urethral pressure profile decreased from 64.1 +/- 17.1 to 51.7 +/- 15.6 cmH2O (p < 0.05) at 2 months after TUMT. The thermotherapy by PROSTCARE is effective in approximately 50% of patients at least 1 year and there were no major complications associated with TUMT during the follow up period.

Aged↗
PubMed1976

[Dynamics of DNA synthesis and blast cell reproduction during formation of the primary immune response and immunologic memory].

A study was made of the dynamics of the DNA synthesis and of the reproduction of the blast cells in the spleen by the methods of autoradiography and radiometry under conditions of a single intervenous immunization of CBA mice with high and low doses of sheep erythrocytes. In the formation of immunological memory stimulated by a subimmunizing dose of the antigen (1-10(5) erythrocytes) cell changes were observed almost exclusively in the periarterial zone; as to the primary response caused by a high dose of the antigen (1-10(9) erythrocytes), it was accompanied by the changes in the cell composition in all the zones of the spleen under study (periarterial, mantle, embryonic centres, red pulp). The maximal accretion of the blast count was observed in the both cases on the second day after the antigen administration. Dynamics of the specific intensity of the 3H-thymidine incorporation into the tissues of the spleen showed the greatest correspondence with the dynamics of the cell changes in the periarterial zone of the spleen.

Animals↗
PubMed1976

[Distribution and excretion of a glycosaminopolysulfate in the rabbit after parenteral application (author's transl)].

The pharmacokinetics of unlabelled and tritium-labelled glycosaminoglycan polysulfate (GAGPS) was examined by gel chromatography, electrophoresis and radiometry. The compound was given i.m. and, for comparison, i.v. In both cases (dose: 7.5 mg/kg) blood levels after 1 h reached maxima of approx. 6 mug/ml and remained between 2.0 and 1.5 mug/ml for between 24 and 48 h. The question of threshold-limited excretion is discussed. The concentration curves of the synovia were almost identical to those of the blood. The cartilage of the joint had a comparable level after 48 h (1.7 mug/g), whilst the level was lower in rib cartilage (1.1 mug/g). Urinary excretion within 24 h amounted to 45% of almost unchanged GAGPS. A further 10% were excreted within the following 24 h. The residue was distributed chiefly in the kidneys, liver, skin, spleen, gut, and bone marrow. In the course of the elimination time the excreted substnace showed a lower molecular weight as was found by gel chromatography.

Animals↗
PubMed1999

Absence of ocular effects after either single or repeated exposure to 10 mW/cm(2) from a 60 GHz CW source.

This study was designed to examine ocular effects associated with exposure to millimeter waves (60 GHz). Rabbits served as the primary experimental subjects. To confirm the results of the rabbit experiments in a higher species, the second phase of the study used nonhuman primates (Macaca mulatta). First, this study used time-resolved infrared radiometry to assess the field distribution patterns produced by different antennas operating at 60 GHz. These results allowed us to select an antenna that produced a uniform energy distribution and the best distance at which to expose our experimental subjects. The study then examined ocular changes after exposure at an incident power density of 10 mW/cm(2). Acute exposure of both rabbits and nonhuman primates consisted of a single 8 h exposure, and the repeated exposure protocol consisted of five separate 4 h exposures on consecutive days. One eye in each animal was exposed and the contralateral eye served as the sham-exposed control. After postexposure diagnostic examinations, animals were euthanized and the eyes were removed. Ocular tissue was examined by both light and transmission electron microscopy. Neither microscopic examinations nor the diagnostic procedures performed on the eyes of acute and repeatedly exposed rabbits found any ocular changes that could be attributed to millimeter-wave exposure at 10 mW/cm(2). Examination of the primates after comparable exposures also failed to detect any ocular changes due to exposure. On the basis of our results, we conclude that single or repeated exposure to 60 GHz CW radiation at 10 mW/cm(2) does not result in any detectable ocular damage.

Animals↗
PubMed1975

Use of the defined antigen substrate spheres system as a model for analysing possible mechanisms of inhibition-blockade of anti-tumour lymphocytotoxicity.

The defined antigen substrate spheres (DASS) system was employed for analysing reactions between solid state antibody or antigen and soluble immune complexes. Sepharose beads covalently coupled with ovalbumin were used to represent tumour cells and beads coupled with antibody against ovalbumin were used to represent anti-tumour lymphocytes; the ovalbumin and corresponding antibody simulated tumour-derived antigen and antibody to tumour respectively. Binding of soluble complexes to the beads was measured by fluorimetry and/or radiometry of fluorescein or 125-I-labelled ovalbumin or antibody. Antigen-antibody complexes in antibody excess bound less effectively to the antibody beads than antigen alone, but complexes in slight or moderate antigen excess bound more effectively. Complexes in antibody excess were most effective in the complex before levelling off and then decreased in extreme antibody excess. The model demonstration of augmentation by antibody of antigen binding to solid state antibody might by analogy reflect a mechanism of inhibition of lymphocyte cytotoxicity. Complexes in a wide range of antibody excess should also be effective in blocking lymphocytotoxicity at the target cell level.

Animals↗
PubMed1975

[Simplified method of radiocardiographic study of central hemodynamics].

The possibility of calculating the main parameters of the cardiac output and the pulmonary blood flow on the basis of a radiocardiogram alone, without performing radiometry of the administered dose of the isotope, and determination of the venous blood activity, is discussed. It is offered to use the relative indices of hemodynamics for this purpose: the indices expressing the values of the minute and stroke volumes, the circulating blood volume in the lungs expressed as percentage of the total circulating blood volume. A high degree of correlation between the absolute and relative indices of the central hemodynamics was established, the advantages and disadvantages of the simplied method of radiocardiography are revealed. The rationale of a parallel determination of the absolute and relative values of the hemodynamic parameters is emphasized since it permits a deeper insight into the hemodynamic shifts.

Blood Volume↗
PubMed2000

[Clinical course of chronic bronchitis in Chernobyl wreckers].

AIM: To characterize clinical symptoms of chronic bronchitis (CB) in Chernobyl wreckers. MATERIAL AND METHODS: 71 CB male Chernobyl wreckers exposed to low-dose radiation and 43 control patients were examined and treated in a specialized hospital in 1988-1996. Clinical features of CB were investigated by clinical (complaints, history, objective examination), laboratory (total blood count, biochemical and immunological blood picture, coagulogram) and instrumental (fibrobronchoscopy, x-ray, radiometry, spirography) findings with further statistical processing. RESULTS: Chernobyl wreckers more frequently had neurocirculatory asthenia and hemoptysis. The latter was caused by bronchial mucosa atrophy. In chronic non-obstructive bronchitis they exhibited mild bronchoobstruction on the distal level. Laboratory indices showed no essential changes. CONCLUSION: Chernobyl wreckers have a more severe course of CB.

Adolescent↗
PubMedDate not supplied

[The state of iodine metabolism in vegeto-vascular dystonia and neurasthenia].

A method of radiometry of the whole body was applied to the study of iodine metabolism in 288 patients directed for examination with a preliminary diagnosis of thyrotoxicosis. The state of iodine metabolism was disturbed in half of them. In 9.1 per cent the changes corresponded to thyrotoxicosis, hypothyroidism. In the rest--disturbances followed the type of dissociation of iodine metabolism, i.e. only one of its phases altered, with a normal value of the rest. A total of 4 dissociation types were noted. The most frequent were the following: normal accumulation of iodine in the thyroid gland in combination with reduced level of organic iodine in the body and increased ioding content in the thyroid gland in combination with the normal organic iodine level in the body.

Adult↗
PubMedDate not supplied

[Potassium metabolism in diabetes mellitus].

A method of radiometry of the whole body in the low-background chamber was applied to the study of the content of total potassium (by K40) in the organism of 67 patients suffering from diabetes mellitus of various severity and in 76 healthy individuals. there was revealed a marked reduction of the total potassium level in diabetics. The more severe the diabetes--the greater the potassium deficiency. Total potassium level had a tendency to normalization after treatment with insulin, potassium salts and vitamins.

Adult↗
PubMedDate not supplied

[Determination of the level of internal irradiation of people farming in territories polluted by radionuclides].

The derived specific activities of radionuclides in the soil are calculated for different pathways of the internal irradiation at a level of an effective dose of 1 mSv per year. The ratio of the actual specific activity to its derived specific activity gives a value of the contribution to annual effective dose for the considered irradiation pathway. The results of the work make it possible to find the upper estimation of the effective dose by simple measurements of the exposure dose rate in a soil sample of a given geometry and by rate of pulses counting by beta- and alpha-radiometry of thick soil samples.

Agriculture↗