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Biomedical subjects

B Bok

Publications and source records attributed to B Bok.

At least 19 recordsLinked to original sources

Sustained hypothyroidism induced by recombinant alpha interferon in patients with chronic hepatitis C.

Thyroid dysfunction has been reported in patients with malignant disease treated with recombinant alpha interferon. Two cases of hypothyroidism in patients with chronic hepatitis C treated with recombinant alpha interferon are reported. In one patient, interferon induced hypothyroidism in the absence of pre-existing thyroid dysfunction and in the other it aggravated a pre-existing thyroid dysfunction. Both patients developed a severe, sustained hypothyroidism requiring thyroxine treatment for one year or more after stopping alpha interferon. Diagnosis of hypothyroidism during treatment can be difficult because of the common side effects of alpha interferon. Thyroid function should be assessed before and during alpha interferon therapy in patients with chronic hepatitis C.

Adult

Dosimetry at the cellular level of Kupffer cells after technetium-99m-sulphur colloid injection.

The radiation dose to Kupffer cells was estimated at the cellular level after intravenous injection of 99mTc labeled sulphur colloids in rats. The results were then compared with those obtained using macroscopic dosimetry. From the microscopy appearance observed using a "track" microautoradiographic method (MAR), it was shown that only 0.2% of the Kupffer cells were actually involved in the pinocytosis of radioactive colloids. For each electronic emission from 99mTc (Auger and internal conversion), the fraction of the emitted energy actually absorbed within the Kupffer cell was calculated using the values provided by Berger. About 15% of the total energy emitted by electrons was absorbed in 0.2% of the Kupffer cells. If these results are extrapolated to humans, the dose absorbed by the labeled cells can be estimated to be between 0.5 and 0.9 Gy/MBq. This represents about 15,000 times the average electron dose to the liver as estimated from macrodosimetric methods. In cases such as this one where an important distribution heterogeneity is expected, dosimetric estimations at a cellular level may be particularly useful.

Animals

Role of technetium 99m methoxyisobutylisonitrile single photon emission tomography in the evaluation of thrombolysis in acute myocardial infarction before and after admission to hospital. Multicenter Study Group "Etude MIBI (EMIBI)".

To investigate initial perfusion status in acute myocardial infarction, methoxyisobutylisonitrile (MIBI) was administered by the rescue physicians. Thirty-nine patients received the radiopharmaceutical at home or upon arrival at the hospital. Diagnosis was confirmed in 30 patients, and 19 emergency thrombolyses were performed. Initial single photon emission tomography (SPET) analysis was constantly abnormal in confirmed myocardial infarction sometimes before direct electrocardiographic signs. MIBI-SPET was normal in non-coronary syndromes. MIBI uptake improved after thrombolysis (P less than 0.001) but also after heparin therapy (P less than 0.05). SPET improvement demonstrated myocardial salvage earlier than wall motion studies. MIBI administration at the patient's home allowed very early perfusion imaging when thrombolysis was performed at home. MIBI-SPET has the potential use of comparing thrombolytic agents or at home versus in hospital thrombolysis.

Ambulances

Pharmacokinetics and biodistribution of technetium 99m labelled standard heparin and a low molecular weight heparin (enoxaparin) after intravenous injection in normal volunteers.

For a better understanding of low molecular weight heparin pharmacokinetics, 99m technetium labelled heparin and enoxaparin were injected intravenously to four normal volunteers, after approval by the Ethics Committee and preliminary animals studies. In vitro and in vivo, the labelled products proved to be stable and identical to the non-labelled drugs. Radioactivity curves in blood, organs and urines were similar for both products. Anti Xa plasma half-life was 3 times longer for enoxaparin than for heparin. Anti IIa plasma half-lives were similar. However, radioactivity persisted much longer than biological activities for both products. After chromatography, most of the radioactivity was bound to AT III, where an anti Xa activity peak was also detected. The anti Xa activity peak seen after adding AT III to plasma was much higher with heparin than with enoxaparin. In urine, biological activities, measured with AT III supplementation, were higher with enoxaparin than with heparin. These results suggest that phenomena other than biodistribution are responsible for the differences in pharmacokinetics observed between these two products. The two most likely explanations are differences in metabolism and/or a release of an endogenous factor.

Adult

[Detection of coronary disease before valve surgery. Contribution of myocardial scintigraphy with dipyridamole].

The detection of coronary disease before valve surgery remains difficult in the absence of coronary arteriography. The contribution of myocardial scintigraphy with dipyridamole (MS-DP) was studied in 34 consecutive patients with valve disease (11 mitral and 23 aortic) with a mean age of 63 +/- 11 years having undergone coronary arteriography before valve surgery. Coronary arteriography was performed because of angina (21 cases) or age (women greater than 50, men greater than 40). Positive criteria of coronary disease were the presence of at least one frank and clearly visible fault of myocardial perfusion (MS-DP positive) and at least one stenosis of greater than 70 per cent by coronary arteriography. Coronary disease existed in 13 patients (38 per cent). Ten patients (29 per cent) had a positive MS-DP. The sensitivity and specificity of MS-DP in detecting coronary disease were 69 per cent and 95 per cent respectively. Its positive predictive value was 90 per cent. MS-DP was negative in all asymptomatic patients (19 per cent of them having coronary disease) and in 11 symptomatic patients (18 per cent of them having coronary disease). The low positive predictive value of angina (52 per cent) increased to 90 per cent when combined with a positive MS-DP. Because of relatively low sensitivity, basing indications for coronary arteriography before valve surgery on the results of MS-DP cannot be advised.

Adult

Pharmacokinetics and tissue distribution of 99mTc-labelled enoxaparin in the rat: evaluation of dosimetry parameters.

A low molecular weight heparin, enoxaparin, was labelled with 99mTc and the characteristics of the labelled compound determined. In vitro the stability, and labelling efficiency (98%) of the labelled drug were excellent. Rats were injected with 99mTc-enoxaparin to study pharmacokinetics and distribution. The results were used to calculate dosimetric estimates which are a prerequisite for pharmacokinetic studies on labelled LMWH (low molecular weight heparin) in human subjects. Biodistribution studies showed preferential liver and spleen accumulation. But the doses absorbed by these target organs remained below the upper limits of the dose received by a patient undergoing hepatic scintigraphy.

Animals

Early isonitrile SPECT in acute myocardial infarction: feasibility and results before and after fibrinolysis.

Early 99Tcm-labelled methoxy-isobutyl-isonitrile (MIBI) SPECT was performed in 14 patients with suspected acute myocardial infarction (AMI). The radiopharmaceutical was administered immediately upon admission to the intensive care unit and before any diagnostic confirmation. Then, if decided, thrombolytic therapy was started. Cardiac imaging was performed 1 h later, and as there is no significant re-distribution, the pictures still showed the pre-treatment MIBI uptake. In three cases acute myocardial infarction was not confirmed. For one of them, the result was normal and this patient was ultimately considered to have had a transient ischaemic event. The two other cases had acute chest pain with a previous history of myocardial infarction (MI) and a pathological MIBI SPECT. In the 11 cases with confirmed first AMI significant perfusion defect was seen. For every patient a new MIBI injection with a control SPECT was repeated 72 h after admission. Eight patients were seen 1 h 15 min to 3 h 15 min after the onset of chest pain and had thrombolytic therapy. Defects were always in agreement with coronary angiography and 2D echocardiography performed in the same period. After thrombolysis, control SPECT showed no recovery in three cases, partial recovery in four, and nearly complete recovery in one. Using this technique, it was then possible to get high quality myocardial perfusion imaging without delaying treatment of AMI. This preliminary series suggests that MIBI SPECT may be useful in accurately showing the size and location of the immediate perfusion defect, and in assessing the response to emergency therapy of AMI, especially thrombolysis.

Adult

Beta-endorphin levels after intrathecal infusion of iodinated contrast media.

Modifications in beta-endorphin levels in cerebrospinal fluid have been described following lumbar puncture and metrizamide injection. Cerebrospinal fluid (CSF) samples were obtained from 19 patients before and after lumbar myelography. Two radioimmunoassays were used. One was a commercial kit; and the other one (developed in our laboratory) used a chromatographic removal from beta-lipotrophin. No definite variation of beta-endorphin was observed after myelography, using either the commercial kit or a more sophisticated procedure. Some controls were prepared by adding metrizamide or Iopamidol in vitro to CSF samples in order to evaluate a non specific effect of these contrast media. The results obtained with these controls suggest that the discrepancy of results may be explained simply by assay artifacts due to drug interferences when using the commercial methods.

Humans

Ten highly sensitive thyrotropin assays compared by receiver-operating characteristic curves analysis: results of a prospective multicenter study.

We report a prospective multicenter study, undertaken to compare the efficacy of 10 highly sensitive thyrotropin assay kits for the diagnosis of hyperthyroidism. Performances of the kits were compared with a reference diagnosis based on clinical examination, pertinent biological tests, and determination by an independent laboratory of the concentrations in serum of free triiodothyronine and free thyroxin. No thyrotropin determination was used in establishing this reference diagnosis. Receiver-operating characteristic curves were obtained for results from 600 patients (217 hyperthyroid and 383 euthyroid) by each kit. Even though analyses were performed out of the working range of most kits, the clinical correlation was nevertheless excellent. The best results corresponded to a sensitivity of 97.5% associated with a specificity of 96.1% and were significantly better than those obtained with all other kits. Results of this comparison depended greatly on the heterogeneity of the "normal"/"abnormal" categories. When only diffuse hyperthyroidism was considered, sensitivity and specificity were improved for all kits, and there was no significant difference among the five best kits.

Humans

Microautoradiographic study of technetium-99m colloid uptake by the rat liver.

A new microautoradiographic technique was developed to study the distribution of 99mTc-labeled radiopharmaceuticals. Using a thick emulsion, it is possible to get microscopically visible tracks of internal conversion and Auger electrons. The liver uptake of microscopic particles has been thought to occur in Kupffer cells but no direct evidence has been provided for technetium colloids. Using this method, 99mTc-labeled colloids were clearly identified in Kupffer cells in the sinusoidal areas of liver. "Track" microautoradiography using a thick emulsion layer may be used on any frozen tissue sections and may provide an important tool to assess the biodistribution of 99mTc radiopharmaceuticals.

Animals

Technetium 99m labelled heparin: pharmacokinetics and tissue distribution in rats after vascular surgery.

Pharmacokinetics of technetium 99m (99mTc) labelled heparin was studied after I.V. infusion (70 IU/kg) in normal rats and in a group of animals just after aortic longitudinal incision and suture. Anticoagulant activity measurements and radioactivity were compared on the same plasma samples. The pharmacokinetic decay of 99mTc-heparin followed a bi-exponential pattern. Half-lives (T1, T2) were significantly shortened after surgery using both techniques. Liver accumulation of labelled heparin was decreased in "sutured" rats and a high uptake of 99mTc-heparin was found on the operated area of the aorta.

Animals

[Experimental arterial microsutures. Evaluation of the risks of thrombosis using technetium 99-labeled heparin].

Following demonstration of a method of assay of circulation heparin by measurement of radioactivity after labelling with 99 m technetium, the technique was used to study effects of arterial microsuture on metabolism of heparin injected postoperatively. Results of a study involving rat aorta showed that local binding was maximum during the first half-hour and that abnormal consumption of heparin continued during the 6 hours following operation. These finding suggest that a risk of thrombosis probably persists throughout this postoperative period.

Animals

[Tomodensitometry and cerebral scintigraphy. Respective indications].

The comparative values of computerized tomography and radionuclide scan for the diagnosis of brain lesions were assessed on a series of 550 patients. A number of indications for each of these two methods have emerged from our results and from those found in the literature. The biases encountered in this type of study are discussed, and a "decision-making flow-chart" is proposed. The procedure of choice is computerized tomography in patients with suspected tumour or intracerebral haematoma, and radionuclide scan in those with suspected subdural haematoma or superficial cerebrovascular disease. The usefulness of clinical examination to determine precisely which of these two methods should be used cannot be overstressed.

Brain

[Microautoradiographic method permitting the study of migration of 99m-technetium labelled leukocytes].

Cell migration studies are very important in inflammatory phenomena. Methods currently used are not quantitative and have been subject to much controversy. Homogeneity of 99mTc leukocyte labelling was verified by a microautoradiographic method (MAR), which was performed in our laboratory. This method was used in cell migration studies to verify if the migrating cells were indeed the labelled cells.

Autoradiography

Technetium 99m autoradiography of labelled white cells.

The cellular uptake of technetium 99m was determined on white blood cells (WBC) by autoradiography, after 'cold' tin pyrophosphate prelabelling followed by pertechnetate labelling. The autoradiographic method gave visible tracks of 99mTc internal conversion and Auger electrons. 75 +/- 5% of the treated WBC were labelled but none of the control WBC. The number and length of tracks per cell varied greatly. This was perhaps due to imaging conditions as well as to variations in cell uptake.

Autoradiography

99m Technetium labelled heparin: potential value as a tracer of heparin activity in pharmacokinetic and biodistribution studies.

Pharmacokinetics and biodistribution of 99m Technetium (99mTc) labelled heparin were studies to assess its value as a tracer of heparin kinetics in comparison with unlabelled heparin. In vitro, the stability and labelling efficiency (98%) of the labelled drug were excellent and elution was minimal. In vivo, after I.V. infusion of the drug, there was no difference in the same animal between anticoagulant activity measurements and radioactive countings, both displaying a plasmatic biexponential pattern (T1 = 2.9 minutes, T2 = 76 minutes). Biodistribution studies showed primarily liver, spleen and kidney accumulation, with no thyroid uptake. The advantages of this technetium labelling may therefore be used for the heparin drug in various experimental and pathological situations even in humans.

Animals