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J T Locher

Publications and source records attributed to J T Locher.

At least 19 recordsLinked to original sources
PubMed2001

Labelled monoclonal antibodies used for the detection of inflammatory processes and and bone marrow metastases.

This review gives a short history of the developments of immunoscintigraphy using radiolabelled monoclonal antibodies and will look at some clinical indications studied in close cooperation with international groups. Examples are presented of infected orthopaedic prostheses and the diagnosis of osteomyelitis in diabetic foot in which the method is considered diagnostically helpful. Furthermore, the accuracy of the bone marrow immunoscintigraphy is discussed in evaluating results of a multi-centre study, clearly demonstrating its diagnostic superiority over bone scanning in metastatic cancer. It is concluded that the future diagnostic trend is going towards more specific agents (antibodies, peptides) and a speedier availability of the diagnostic results in cases of supposed infection.

Journal Article↗
PubMed1996

Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography.

There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging. 52mMn can be produced in a 52Fe-52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate 52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-based K1 values were correlated with microsphere blood flow. The models consisted of one (K1, k2) and two (K1, k2, k3) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations: K1=1.152 flow+0.059 (r=0.92), R=0.069 flow+0.034 (r=0.84). Based on these regressions, K1 increased 2.7-fold and R 2.6-fold in the examined flow range of 0.5-2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that 52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.

Animals↗
PubMed1995

Experience with the iodine-123 and technetium-99m labelled anti-granulocyte antibody MAb47: a comparison of labelling methods.

Four different methods of radiolabelling the anti-granulocyte monoclonal antibody MAb47 were compared and their influence on diagnostic value studied. The best clinical images were obtained following labelling with iodine-123 by the Iodogen method and direct labelling with technetium-99m after tris-(carboxyethyl)-phosphine treatment of MAb47 to achieve disulphide bridge reduction. 99mTc labelling using a specific ligand (MAb47-mtp), or a second method involving direct reduction with mercaptoethanol, led to an increased background activity in clinical studies, thus impeding the diagnosis of chronic disease. Fresh infections were clearly localized by all four preparations. The elimination of the activity from the blood was slower in the case of the iodinated MAb47, while the collected urine samples showed an excretion of about 10% of the injected activity per day independent of the labelling method. The results in terms of sensitivity and specificity were rather similar for all labelling methods and ranged from 90% to 99%.

Abscess↗
PubMed1995

Myocardial 18F-FDG-PET. Experiences with the euglycemic hyperinsulinemic clamp technique.

Myocardial positron emission tomography (PET) with 18F-Fluordeoxyglucose (FDG) is increasingly used for the detection of viable tissue in the infarcted myocardium. Previous studies show that the variable metabolic conditions determine the regional distribution of this tracer and that the inhomogeneities of uptake often observed even in the normal myocardium may relate to substrate availability. The authors tried to stimulate the myocardial FDG uptake by either the technically easier method of glucose loading or by the euglycemic hyperinsulinemic clamp (EHC) technique. In their hands both methods could be considered as equally practicable but differing in some important details in regard to both the study protocol (tracer dose, optimal scanning time) and the reproducibility of results. The EHC allows a quick stabilization of the metabolic environment and resulted in an earlier and markedly increased FDG uptake. However, the important standardization of the method was performed by a computer-controlled system only for the glucose and insulin infusions. Their experiences show that the EHC provides a useful framework for assessing altered cardiac metabolism and possibly describes changes after therapeutic interventions more precisely than the commonly used glucose-loading technique.

Deoxyglucose↗
PubMed1995

[Determination of three body compartments in the chest by scintigraphy].

We adapted a previously described method for the measurement of transthoracic tissue thickness and volumes of blood and interstitial tissue. This non-invasive procedure can be performed safely and by relatively simple means. We used a gamma camera and 99mTc to obtain transmission and emission scintigrams. A computer program written for a personal computer, can recognize the borders of the lung in a fully automatic manner and do the necessary calculations. Clinical studies show significantly higher interstitial volumes of the lung in patients with chronic pulmonary sarcoidosis.

Gamma Cameras↗
PubMed1993

Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET).

The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice. After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50-60% after 24-36 h and disappeared within 6 days. After doses of 0.1 mg to 0.5 mg, D2 receptor occupancy in the putamen and caudate nucleus increased from 20 to 70% 3-7 h after administration and amounted to 40 to 75% at the peak time (20-29 h). This suggests that cumulative D2 receptor blockade would occur if equal or increasing doses of savoxepine were given repeatedly. Extrapyramidal adverse-effects would be likely to occur under such circumstances. An adequate test of the theory that preference for hippocampal dopamine D2 receptors with afford a good therapeutic ratio requires an alternative dosing regimen.

Adult↗
PubMed1992

[Evaluation and documentation of tomographic images and further data using the Apple-Macintosh PC].

Use of the personal microcomputer for the analysis of clinical cardial PET studies acquired at the Paul Scherrer Institute in Villigen, Switzerland. At present this is the only PET facility in Switzerland. As the local computers were not usually available for image analysis, it was necessary to find a convenient way to visualize and analyze the PET images in our department in the Cantonal Hospital, Aarau (distance to Villigen some 30 km). The personal microcomputer is, as other authors have already shown, in fact capable of handling the acquired images (128 by 128 pixels) easily. We use a Macintosh IIcx (16 MHz Motorola 68030 CPU) as image analysis workstation. In spring 1990 we implemented a software which could read the original Siemens matrix file directly into the Macintosh PC. As the handling of this software was somewhat clumsy, we now use a very powerful software ("Explorer", UCLA), which is specially designed for PET analysis. Analysis of PET data on the personal computer saves both time and money as we are able to use a standard PC periphery, which is less expensive than specially designed medical units.

Heart↗
PubMed1988

Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.

Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.

Animals↗
PubMed1988

Immunoscintigraphic localization of inflammatory lesions: clinical experience.

This clinical study was based on the experimental results reported in the two preceding papers, showing that the highly selective affinity of the 123I-anti-CEA monoclonal antibody 47 (123I-Mabgc) for human granulocytes makes this compound suitable for the immunoscintigraphic detection of inflammatory lesions. Forty five patients with suspected infections have been studied after infusion of 4 mCi (148 MBq) 123I-Mabgc corresponding to 120 micrograms labeled protein. No adverse reactions have been seen. Because of the high number of labeled cells, the quality of the images was excellent. SPECT was performed in 15 cases in order to define the extent of the lesion. Infectious foci were usually seen 3-5 h postinjection, but the unimpaired function of the granulocytes guarantees diagnostically relevant examinations over a much longer period of time. Scans were read as being negative if no pathological accumulation of activity was detected after 24 h. The new scanning method is technically easy to perform and provides distinct advantages over other techniques necessitating in vitro labeling of the white blood cells. Therefore, recommended indications are acute infections of unknown origin or extent, especially recurrent episodes of osteomyelitis and infections of joint prostheses.

Adolescent↗
PubMed1988

Immunoscintigraphic localization of inflammatory lesions: pharmacokinetics and estimated absorbed radiation dose in man.

Five patients with inflammatory lesions received anti-granulocytes murine monoclonal antibody (Mabgc) infused over 5 to 15 min at doses between 3.4 and 5.4 mCi 123I (120 micrograms antibody). Clearance of 123I from blood pool closely fits a biexponential mathematical model with the two effective half-lives 0.73 h and 9.3 h. The spontaneous release of 123I was found to be relatively low in the blood pool. The cumulative urinary excretion of the 123I label over 120 h was in the range of 63% of the totally administered dose and is assumed to represent only a low molecular compound or 123I alone as iodide. Analysis of the label in spleen, liver and red marrow showed that the concentration of label in these tissues remains more or less constant over a period of 20 h after infusion. With data of liver, spleen, red marrow and whole body activity over a period of 24 h, an estimated radiation dose was calculated. Compared with 111In labelled leucocytes, especially in spleen, the absorbed dose is lower by a factor of ten per examination.

Animals↗
PubMed1986

Imaging of inflammatory and infectious lesions after injection of radioiodinated monoclonal anti-granulocytes antibodies.

Successful detection of inflammatory lesions by planar scintigraphy and SPECT after injection of iodine-123 labelled monoclonal antibodies directed against human granulocytes (123I-Mabgc) is demonstrated. This new tracer has been compared with indium-111 labelled white blood cells (111In-WBC) in selected patients with proven infectious lesions. Scans were equally positive in all cases, but the methodical advantages of the new marker were obvious, namely, there is no need for cell separation and the images of inflammatory lesions were better defined. In addition, SPECT could be performed with 123I-Mabgc and allowed a better anatomic localization and a three-dimensional description of the lesions. No adverse reactions have been seen. It is concluded, therefore, that 123I-Mabgc is a promising agent for the detection of acute focal inflammatory lesions which may, with advantages, replace 111In-WBC.

Antibodies, Monoclonal↗
PubMed1985

[Familial deficiency of thyroxine-binding globulin].

A family with congenital athyropexinemia is reported. By reconstruction of the family tree over seven generations, a heterozygous woman born in 1842 was identified as the first carrier of the anomaly who introduced the disorder into two family branches by marrying twice. 24 descendants examined included 6 heterozygous females and 8 hemizygous males. All were euthyroid. The mode of inheritance was obviously linked to the X-chromosome. An interesting fact was that in one family thyroxine binding globulin was absent or measured only in traces in hemizygous patients.

Female↗
PubMed1979

Experimental approach to the correlation of hemodynamic changes with increases in urinary lactate dehydrogenase as a new parameter reflecting serious renal tissue damages.

From previous investigations with nephroptotic patients increased urinary LDH was assumed to be a reliable marker indicating a renal tissue defect due to the organs descent in erect position. Animal experiments now allowed correlation of this enzymatic activity with controlled changes of anatomical and physiological parameters. Changes of the renal hemodynamics or urinary flow induced in acute experiments in dogs simulated kidney displacement in nephroptotic patients. Both ureters were cannulated for separate urine collection and one kidney was manipulated. The renal arterial or venous flow was reduced or the ureter was occluded under electromagnetic blood-flow control. Arterial constriction alone (30%/15 min) selectively caused a drastic decrease (approximately 80%) of Xenon wash-out (= nutrient-flow) in the renal cortex. Under the same conditions radio-labeled microspheres injected intracardially showed a centralization of the renal capillary blood flow from the outer cortex to the juxtamedullary zone. Urinary LDH activities increased up to 800% immediately after arterial constriction. In accordance with total LDH activity the percentage distribution of isoenzymes changed: LDH-I increased and the LDH-V decreased. Neither constriction of the renal vein nor ureteral occlusion had similar effects. In long-term experiments backward fixation of one kidney in rats would reflect the effects of kidney displacement over years in nephroptotic patients: animals were unilaterally nephrectomized and the remaining kidney was dislocated backwards (approximately 2,5 vertebrae) and fixed to the lateral pelvic wall. "Ptotic" rats showed during the following examinations a constant increase of urinary LDH up to 50% by 26 weeks postoperatively. In accordance with increased LDH the isotope nephrogram was pathological and arteriographies showed a stretched and narrowed renal artery. In a number of rats "ptotic" fixation was not effective enough. All these animals showed normal LDH, isotope nephrograms and arteriographies. Both animal experiments documented that reduced flow/hypoxia is essentially responsible for the tissue damage in the kidney manifested by increased release of urinary LDH.

Animals↗
PubMed1979

Diagnostic relevance of urinary lactate dehydrogenase determination in nephroptosis and for the indication to nephropexy.

Previously reported experiments with animals suggested that reduced renal arterial flow might be the actual cause for the pathogenicity of nephroptosis. Clinical studies now give evidence that measurements of urinary LDH may be a criterion equal to the isotope nephrogram (ING) in considering this disease. Patients with a "mobile" kidney verified by i.v. pyelography were examined by an ING and a 1-day test for urinary LDH. In accordance with periodic kidney displacement total urinary LDH activities were measured in a 8-h urine volume in the supine position and a 8-h urine volume in the erect position of the patients. Evaluations were all expressed as percentage increase of LDH activity of the patient in the erect versus supine position and correlated with his ING-pattern. Among 45 nephroptotic individuals 34 showed, in accordance with a pathological ING, a mean LDH increase of more than a 100%. Eleven individuals had normal INGs and less than 20% increase equal to a group of 16 normal controls. We postulated a 30% increase as the upper limit between normal and pathological urinary LDH. The percentage distribution of isoenzymes was also altered within the pathological LDH range: LDH-I, which increases in normal controls, now decreased in nephroptotic patients. LDH-IV and V, which decrease in controls, now increased. Homomeric isoenzymes obviously show reciprocal behavior. The degree of kidney descent in cm does not correlate with percentage increase of urinary LDH, i.e. it is not a criterion for pathogenicity. Biopsies taken during nephropexy revealed that from an anamnestic duration of 50 weeks onwards the kidney is significantly affected and tissue damages become evident. If patients were re-investigated after nephropexy they showed normal i.v. pyelograms and normal LDH and no longer had clinical symptoms.

Humans↗
PubMed1977

Tumor calcinosis imaged by bone scanning: case report.

The typical symmetric lesions in a patient with tumor calcinosis avidly accumulated bone-seeking compounds. Thus, bone scanning is very helpful in the diagnosis of this rare disease, especially if the calcareous masses are not situated periarticularly.

Calcinosis↗