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Biomedical subjects

V John

Publications and source records attributed to V John.

At least 55 records · Page 3Linked to original sources

[Digital luminescence radiography (DLR) for skeletal diagnosis in traumatology].

170 patients who had suffered trauma to bones or soft tissues were examined by a digital and a conventional film/screen technique. In addition to "standard" and edge-enhanced images, post-processing was carried out and compared with conventional radiographs. Four radiologists and two surgeons evaluated the compacta, spongiosa, soft tissues, fractures and osteo-synthetic materials as shown on the two systems. The "standard" digital images are inferior to film images, but edge-enhanced images showed definite advantages for demonstrating soft tissues. Evaluation of osteo-synthetic material is limited by the creation of artifacts. Recognition of detail can be significantly improved by using post-processing with optimized parameters.

Adolescent↗

Free radicals in children with rheumatic diseases in serum and synovial fluid.

Free radicals, demonstrable by thiobarbituric acid, are also significant in the pathogenic concept of juvenile chronic arthritis. 41 patients without therapy demonstrate significantly increased values in serum, compared with the same patients after a treatment of 4 weeks. There are relations between ESR and the concentration of thiobarbituric acid reactive substances in serum, but without statistic significance. In the synovial fluid the radicals are increasingly demonstrable, but there is no relation to the number of cells or granulocytes.

Arthritis, Juvenile↗

Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat.

By a sensitive and quantitative fluorometric assay, brain and plasma time-dependent concentration profiles were generated for phosphoramide mustard (PM) and active alkylating metabolites derived from cyclophosphamide (CPA) administration to rats. Whereas PM rapidly disappeared from plasma, with a monophasic half-life of 15.1 min, equimolar administration of CPA generated active metabolites in plasma that disappeared monoexponentially, with a composite half-life of 63 min. As a consequence, the time-dependent concentration integral of active alkylating metabolites derived from CPA administration, calculated between 5 min and infinity, was 3-fold that of PM. Pharmacokinetic parameters were calculated for each compound. The brain/plasma concentration-integral ratios of PM and active alkylating metabolites derived from CPA were 0.18 and 0.20, respectively. The cerebrovascular permeability-surface area product of PM was 7.5 x 10(-5) s-1, which is similar to that of other water-soluble anticancer agents that are restricted from entering the brain. The activities of a range of daily doses of PM and CPA were assessed against subcutaneous and intracerebral implants of Walker 256 carcinosarcoma tumor in rats. Inhibition of subcutaneous tumor growth by 50% was caused by CPA and PM doses of 6.6 and 12.0 mg/kg (daily for 5 consecutive days, starting 36 h after tumor implantation), respectively. However, administration of daily doses of up to 40 mg/kg did not significantly increase the survival of animals with intracerebral tumor implants. These studies indicate that active metabolites of CPA are restricted from entering the brain and that only subtherapeutic concentrations are achieved in brain tissue after systemic administration of CPA or PM.

Animals↗

Differences in the recovery of right and left ventricular function after ischaemic arrest and cardioplegia.

Differential susceptibility of right (RV) and left (LV) ventricles to plain ischaemia and the contribution of cardioplegia in reducing the ischaemic damage was evaluated in a sheep model of cardiopulmonary bypass. Sheep (n = 16) were equally divided for the two protocols of the study. Each sheep served as its own control. RV and LV functions were studied and compared by plotting ventricular function curves (Starling and Sarnoff). The mathematical centre of mass (COM) for each curve was computed by a polynomial regression program. The COM values of the contractility indices [stroke volume (SV), stroke work (SW)] represented ventricular heterometric reserve. RV and LV heterometric reserve was significantly (P less than 0.01) reduced after 1 h plain ischaemia, and quantitatively this change was more for RV than for LV (P less than 0.05). As compared to LV, a significantly greater reduction in RVSW was brought about by a significantly (P less than 0.01) greater reduction in RVSV, because there were no significant differences between the post-ischaemic recovery in the RV and LV afterloads. Cardioplegic protection nearly normalized filling pressure and contractility (SV, SW) of both ventricles, but major differences were observed in the recovery of compliance. Recovery in the RV compliance exceeded the control values, and quantitatively the recovery in RVSW was slightly more than in LVSW. The results of this study indicate that the RV suffers more damage from plain ischaemic arrest and hence benefits more from the cardioplegic protection.

Animals↗

Intra- and intersubject variability: mixed-effects statistical analysis of repeated doses of an angiotensin converting enzyme inhibitor, CGS 16617.

The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components of variance were evaluated for a mixed-effects statistical model in which subjects were regarded as a random factor. While intersubject variability was statistically significant (P less than 0.05) for all pharmacokinetic variables measured, AUC, Cmax, t1/2, and tmax, its contribution to the total observed variability was relatively small for AUC, t1/2, and tmax. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, Cmax, t1/2, and tmax, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.

Adult↗

Gastrointestinal transit of a solid indigestible capsule as measured by radiotelemetry and dual gamma scintigraphy.

The objectives of the present study were to evaluate gastric and small bowel transit times of an indigestible solid matrix and to characterize the specific changes in intraluminal pH as a function of transit time through the gastrointestinal tract. Particular attention was paid to the lag time at the ileocecal junction. A Heidelberg capsule (HC), labeled with 10 microCi Indium-111, was given orally to six healthy male subjects 15 min after oral ingestion of 100 microCi of 99mTc-sulfur colloid as a liquid fatty meal (4 ml/kg). Intraluminal pH was monitored continuously via the HC. Gastric and small bowel transit of the radionuclides was monitored via external scintigraphy at 0.5-hr intervals. Gastric residence times (GRT) of the HC ranged from 2.8 to 4.8 hr. with a mean (+/- SD) of 3.6 +/- 0.8 hr. These values were independent of the individual's weight, height, or body surface area. Small bowel transit times of the HC ranged from 2.8 to greater than 5.5 hr. which were consistent with the reported values of 3 to 5 hr. The lag times of the HC at ileocecal junction ranged from 0.8 to greater than 2.5 hr. The presence of the lag times at the ileocecal junction in all subjects confirmed that it acts as a valve or sphincter. Mouth-to-cecum transit times of the HC occurred within 9.0 hr in 50% of the subjects. In general, following a sharp rise upon pyloric passage of HC the pH dropped slightly but then increased linearly throughout the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Difluorothromboxane A2 and stereoisomers: stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels.

The present study reports on the selective effects on human platelets and canine saphenous veins of four stable difluorinated analogues and thromboxane A2 (TXA2), in which the characteristic 2,6-dioxa[3.1.1]bicycloheptane structure of TXA2 has been retained. The four compounds differ in their stereochemistry of the 5,6 double bond and/or the 15-hydroxyl group. Only 10,10-difluoro-TXA2 (compound I) with the natural stereochemistry of TXA2 was an agonist in both platelets and canine saphenous veins (EC50 = 36 +/- 3.6 nM and 3.7 +/- 0.8 nM, respectively). (15R)-10,10-Difluoro-TXA2 (compound II), (5E)-10,10-difluoro-TXA2 (compound III), and (5E,15R)-10,10-difluoro-TXA2 (compound IV) were antagonists of platelet aggregation stimulated by compound I (Kd = 98 +/- 46 nM, 140 +/- 42 nM, and 1450 +/- 350 nM, respectively). However, compounds II, III, and IV stimulated contraction of canine saphenous veins (EC50 = 36 +/- 4.4 nM, 31 +/- 6.8 nM, and 321 +/- 50 nM, respectively). All four compounds could displace the TXA2/prostaglandin H2 antagonist 9,11-dimethylmethano-11,12-methano-16-(3- 125I-4-hydroxyphenyl)-13,14-dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2 from its platelet receptor (Kd values = 100 +/- 30 nM, compound I; 280 +/- 60 nM, compound II; 230 +/- 70 nM, compound III; and 1410 +/- 1020 nM, compound IV). These results support the existence of two subtypes of TXA2/prostaglandin H2 receptors and emphasize the importance of the stereochemical requirements of these TXA2 analogues for interaction with these receptors. These stable fluorinated TXA2 analogues should prove useful tools for the further characterization of these and other TXA2/prostaglandin H2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Preservation of left ventricular function during coronary artery bypass graft surgery.

Effects of hypothermic potassium cardioplegia on left ventricular performance and myocardial damage were assessed in 35 patients undergoing coronary artery bypass surgery. Hemodynamic data and enzymatic evidence of left ventricular ischemic damage were examined and compared in the immediate postoperative period. Left ventricular stroke work index showed a significant depression during the first hour with gradual recovery and a significant increase after 24 h. Myocardial specific isoenzyme creatine kinase (CK-MB) showed a very good nonlinear relationship with stroke work index within the whole range, whereas lactate dehydrogenase isoenzyme (LDH-I) had no relationship with the stroke work index. There was a high incidence of transient postoperative arrhythmias and electrical activity took a long time to stabilize. Left ventricular ultrastructure was generally well preserved. The results of this study demonstrate adequate structural and functional preservation of left ventricle by hypothermic potassium cardioplegia.

Adult↗

CT scanning of the breast in problem cases.

This is a report of the experience with 200 patients who during 1981 to 1984 underwent breast scanning on a conventional body scanner. Pre- and post-contrast scans of the breast were obtained. A postcontrast enhancement of 50 HU and more turned out to be specific for malignant lesions. Radiation dose to the breast was in the same range as with high filtration xeromammography and high resolution film-screen mammography with additional grid. Breast scanning is recommended in cases in which mammography alone is of limited value, including dense fibrocystic breasts in women at high risk, follow-up in breast cancer patients after breast conserving therapy, in patients with silastic implants and in the follow-up of breasts with huge scars due to multiple biopsies.

Adolescent↗

[Radiological diagnosis of late effects on thoracic organs after chemotherapy and/or radiation therapy as well as after radionuclide therapy].

With respect to the considerable risk involved in oncologic therapy methods, especially when bleomycin is administered, a specific observation of the possibly fatal side effects is necessary. As, for example, a regression of pulmonary alterations caused by bleomycin is possible when they are detected early, the call for early recognition of developing lesions is becoming more and more urgent. Conventional radiologic diagnosis is scarcely important in early recognition, but X-ray computed tomography is a suitable imaging method because it is able to visualize tiny intrapulmonary and pleural alterations. The CT image of bleomycin pneumopathy is variable. There are irregular, partly sharply defined nodular structures. They are generally found in peripheric sites near to the pleura with the exception of the pleura mediastinalis. Contrary to functional investigations such as the determination of the CO diffusion capacity which are equipment- and cost-consuming, X-ray computed tomography does not only offer a qualitative information on an existing pneumopathy, but provides also a precise localization of these pulmonary alterations. Computed tomography is a method for the quantitative assessment of the peripheral lung density with the same amount of information as the measurement of the gas transfer per pulmonary volume unity. However, it offers the advantage of a simultaneous qualitative visual judgement of the organ, i.e. not only the types and dimensions of pulmonary lesions can be assessed, but the physiologic effect of these lesions, i.e. the pulmonary function, can be determined by quantitative density measurement, too. Thus quantitative computed tomography represents an alternative in the assessment of the pulmonary function. According to the recommendations of Bellamy et al., it should be combined to routine computed tomography of the thorax. The method of choice for the diagnosis of anthracycline cardiotoxicity is radionuclide ventriculography. A decrease of the left ventricle expulsion to less than 45% is considered as a critical value. However, cardiac side effects of cytostatic drugs can be detected early in the individual course, so that late effects in the sense of irreversible cardiomyopathy are prevented.

Adult↗

[Computed tomography guided positioning of catheters for temperature measurement in hyperthermia of malignant tumors].

Prior to a combined treatment with ionizing radiation and hyperthermia, 38 patients with superficial, semi-deep, and deep tumors received catheters for temperature measuring probes which were introduced under CT control. After having established a localization diagnosis and determined the angle for the puncture as well as the length of the puncture canal, a puncture needle containing a closed teflon catheter was introduced subsequent to local anaesthesia and puncture incision of the skin. None of the patients needed a general analgetic and sedative treatment. 10% of the patients presented a dislocation making necessary a reimplantation. Local infections at the catheter insertion point were observed in three cases, a phlegmonous inflammation was seen only in one patient who had undergone an immunosuppression by means of cytostatic drugs. In one patient a temporary bleeding led to a slight haemoglobin reduction which, however, did not require further therapeutic measures. The insertion of catheters for intratumoral temperature measurement was well tolerated by the patients. It could be performed in out-patients with good general condition and no further risk factors.

Adolescent↗

Inhibition of platelet aggregation by novel triphenylethylene analogs.

The present study has evaluated the effect of some newly synthesized triphenylethylene (TPE) analogs on platelet arachidonic acid metabolism and function. All compounds tested inhibited arachidonic acid induced platelet aggregation and several were superior to aspirin in their relative potency. Introduction of a carboxyl function into the alpha-ring, which should enhance binding according to proposed structural models for cyclooxygenase inhibitors, was not found to be beneficial. Increased structural rigidity, which resulted from covalent linkage of two aromatic rings in this series, did not eliminate anti-aggregatory properties.

Adult↗

[Somatic radiation risk to the breast under different radiological research procedures].

This paper deals with radiation risk in terms of somatic dose index from different mammographic techniques (Xeromammography, Screen-film-mammography alone or with additional grid, and industrial film mammography) and from various non-mammographic radiodiagnostic procedures with the breast partially or totally exposed to the x-ray beam, e.g. tomography of the lungs and dorsal spine, fluoroscopy, angiography, and computerised tomography of thoracic organs.

Angiography↗

Inhibition of cyclooxygenase mediated by electrochemical oxidation of gentisic acid.

Prostaglandin synthase (EC 1.14.99.1, 8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase), commonly referred to as cyclooxygenase, was inhibited irreversibly upon application of a fixed oxidative potential (+0.4 V versus saturated calomel electrode) in the presence of the aspirin metabolite gentisic acid (2,5-dihydroxybenzoic acid). Electrolyses were carried out at 0 degrees C in a phosphate buffer solution (pH 7.2, 0.1 M) using a carbon felt electrode. This electroinactivation process was time-dependent and pseudo first-order with respect to gentisic acid at concentrations up to 300 microM. These concentrations of gentisic acid are below those normally reported to be inhibitory. The enzyme was stable to this applied potential in the absence of gentisic acid. Similar treatment of apoenzyme (heme-removed) revealed no loss in catalytic activity after reconstitution to the holoenzyme. Oxyphenbutazone, a nonoxidizable competitive inhibitor of cyclolooxygenase, was observed to protect the enzyme from electrolytic inactivation mediated by gentisic acid. Radiolabeling studies indicated the covalent attachment of approximately 1 eq of gentisic acid/subunit of enzyme. These studies support the possible role of quinonoid intermediates in the observed anti-inflammatory action of salicylate derivatives.

Animals↗

Electrolysis-mediated irreversible inactivation of lipoxygenase directed toward electroaffinity labelling.

Irreversible inhibition of soybean lipoxygenase-1 (SL-1) was accomplished via a controlled potential oxidative electrolysis of 1,5-dihydroxynaphthalene (1,5-DHN) at +0.8 V vs SCE. The inactivation of SL-1 with this known inhibitor was greatly enhanced under these electrolytic conditions to which the enzyme itself was stable. Electrolyses were run at 0 degree C in a 0.05 M phosphate buffer, pH 7.0, using graphite cloth electrodes. The rate of inactivation was observed to be limited by and dependent on the anodic oxidation of 1,5-DHN. The non-oxidizable (at this potential) inhibitor indomethacin was shown to protect the enzyme from irreversible inactivation, however, an external nucleophile (2-mercaptoethanol) had little effect. These initial studies support the capability of such electrochemical methods for the site-specific covalent modification (affinity labelling) of lipoxygenase, and perhaps other enzymes.

Electrochemistry↗

Radiation exposure in high resolution computed tomography of the spine.

From all the available radiodiagnostic procedures for diagnosing spinal disorders (conventional tomography, myelography, CT), high-resolution, thin-slice computer tomography presents the highest radiation exposure as represented by the somatic dose index. It allows, however, the retrospective computer reformatting of axial slices into secondary slices of any projection desired. To obtain this extra information with conventional tomography would require further exposures in the desired projections and/or thinner slices. But there is a great amount of important diagnostic information that plays a decisive role in the choice of the form of therapy and the preoperative planning of surgical which cannot be obtained by conventional radiological procedures.

Bone Marrow↗

CT imaging in lumbar disc disease. The value of multiplanar reconstructions.

A CT/T 8800 (General Electric) CT scanner was used to study lumbar disc disease in fifty patients. In seven patients so-called computed tomography metrizamide myelography was performed, whereas in the remaining cases no contrast enhancement was used. Multiplanar reconstructions were done. Irradiation exposure was measured during the investigations and compared with data during conventional myelography. We found that lumbar CT scanning is not a screening method in cases of lumbar disease, but the aimed use gives further information about the underlying process and its differential diagnosis. Multidirectional reconstructions reduce the number of diagnostic errors. This procedure does not increase the radiation exposure dose in comparison with conventional myelography.

Adult↗