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Biomedical subjects

F Wolf

Publications and source records attributed to F Wolf.

At least 91 records · Page 5Linked to original sources
PubMed1993

Use of immunoscintigraphy in the diagnosis of fever of unknown origin.

Fever of unknown origin (FUO) has been defined as an elevation in temperature (38 degrees C) for at least 2-3 weeks despite intensive investigation. The value of immunoscintigraphy with the technetium-99m-labelled anti-granulocyte antibody anti-NCA-95 (BW 250/183, IgG1) was studied retrospectively in 34 consecutive patients with FUO. Every effort was made to confirm a diagnosis, including methods such as ultrasonography, computed tomography, magnetic resonance imaging, bacteriological tests, surgical intervention and clinical follow-up. In 58.8% of the patients, an infectious cause for the fever was found, in 30.2% of the patients, a benign or malignant haematological disease, pancreatitis or thyrotoxicosis was found. No cause for fever could be found in 11%. The overall diagnostic sensitivity and specificity of immunoscintigraphy for infection were 40% and 92% respectively. The positive predictive value was calculated to be 88% and the negative predictive value was calculated to be 52%. False-negative scans were especially noted in patients with endocarditis, pneumonia and small brain abscesses, where the lesions did not exceed a diameter of 0.5 cm. If patients with endocarditis were excluded, the imaging sensitivity and specificity were increased to 57% and 95%. This study demonstrates that 99mTc-anti-NCA-95 scanning is able to localize infectious causes of FUO, other than endocarditis.

Adult↗
PubMed1993

Comparison of 99Tcm-labelled specific murine anti-CD4 monoclonal antibodies and nonspecific human immunoglobulin for imaging inflamed joints in rheumatoid arthritis.

Inflamed joints in human rheumatoid arthritis (RA) can be imaged employing 99Tcm-labelled anti-CD4 monoclonal antibodies (MAbs). These MAbs recognize the CD4 molecule expressed on T-helper cells and, with a lower density, on macrophages, which are both abundantly present in RA inflammatory infiltrates. However, it is at present unclear whether specific binding to target molecules in the inflamed joint determines the joint uptake of anti-CD4 MAbs, i.e. whether the uptake of anti-CD4 MAbs differs from that of control immunoglobulins with irrelevant specificity. Eight patients with severe, active RA were examined after intravenous injection of a 99Tcm-labelled murine anti-human CD4 MAb (MAX.16H5; 200-300 micrograms, 370-550 MBq) or polyclonal human immunoglobulin (HIG; Technescan, MDH-67, Mallinckrodt Diagnostica; 1 mg, 370 MBq); five patients received both the anti-CD4 MAb and HIG. Whole body and joint scans in anterior and posterior views were obtained 1, 4 and 24 h after injection. As early as 4 h after injection, the anti-human CD4 MAb showed a higher target-to-background ratio in arthritic knee and elbow joints in comparison to polyclonal HIG used for conventional imaging, indicating that that anti-CD4 MAb allows more specific detection of inflammatory infiltrates rich in CD4-positive cells.

Adult↗
PubMed1993

Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker).

Generalised myotonia Becker (GM) is an autosomal recessively inherited muscle disorder. Affected subjects exhibit myotonic muscle stiffness in all skeletal muscles with marked hypertrophy in the legs. A transient muscle weakness is particularly pronounced in the arms and hands and is a typical symptom of the disorder. Recently, we showed complete linkage of the disorder GM to the gene (CLCN1) coding for the skeletal muscle chloride channel CLC-1 and the TCRB gene on chromosome 7 in German families. In the study presented here we performed linkage analysis on 14 new GM families. The GM locus was again completely linked to both the CLCN1 and the TCRB gene in all families with a combined lod score of Z = 9.26 at a recombination fraction of theta = 0.00. This confirms our previous data and supports the hypothesis that GM is a genetically homogeneous disorder. The previously detected T to G missense mutation is found on 15% of the 66 GM chromosomes counted so far.

Alleles↗
PubMed1993

Joint uptake and body distribution of a technetium-99m-labeled anti-rat-CD4 monoclonal antibody in rat adjuvant arthritis.

Joint uptake and body distribution of a 99mTc-labeled monoclonal antibody (Mab) to the rat CD4 molecule (W3/25; IgG1) were investigated after intravenous injection in normal rats and in animals with experimentally induced adjuvant arthritis. An isotype-matched Mab with irrelevant specificity (anti-human carcino-embryonic-antigen) was used as control. A 4 hr sequential gamma-camera imaging revealed that both anti-CD4 and control Mab accumulated to a higher degree in arthritic than in normal ankle joints; the accumulation was comparable for the two Mabs. In contrast to the inflamed joints, a specific accumulation of the anti-CD4 Mab was found in organs rich in CD4-positive cells, i.e. spleen, bone marrow and lymph nodes, as assessed by direct well counter measurements 16 hr after injection. The control Mab displayed no preferential organ accumulation in either normal or diseased animals. These results indicate that a specific accumulation of anti-CD4 Mabs occurs in CD4-positive-cell-rich tissues in both normal and diseased animals and that immunoglobulins accumulate preferentially in inflamed joints regardless of their antibody specificity.

Animals↗
PubMed1992

The skeletal muscle chloride channel in dominant and recessive human myotonia.

Autosomal recessive generalized myotonia (Becker's disease) (GM) and autosomal dominant myotonia congenita (Thomsen's disease) (MC) are characterized by skeletal muscle stiffness that is a result of muscle membrane hyperexcitability. For both diseases, alterations in muscle chloride or sodium currents or both have been observed. A complementary DNA for a human skeletal muscle chloride channel (CLC-1) was cloned, physically localized on chromosome 7, and linked to the T cell receptor beta (TCRB) locus. Tight linkage of these two loci to GM and MC was found in German families. An unusual restriction site in the CLC-1 locus in two GM families identified a mutation associated with that disease, a phenylalanine-to-cysteine substitution in putative transmembrane domain D8. This suggests that different mutations in CLC-1 may cause dominant or recessive myotonia.

Amino Acid Sequence↗
PubMed1992

Assessment of cardiac adrenergic supply in mitral valve prolapse using m-[123I]iodobenzylguanidine scintigraphy.

Presynaptic as well as postsynaptic adrenergic regulation abnormalities are reported in symptomatic patients with mitral valve prolapse. This study was undertaken to evaluate presynaptic sympathetic supply by m-[123I]iodobenzylguanidine scintigraphy in 17 preselected patients with mitral valve prolapse and symptoms suggestive of hyperadrenergic dysautonomia as compared to normal scintigraphic findings. Mitral valve prolapse was echocardiographically proven within the left parasternal long axis view. Percentual activity of m-[123I]iodobenzylguanidine in 33 sectors of all oblique slices along the short axis was calculated relative to the maximal uptake, set at 100%. In general, no significant differences of mean values of sectoral quantitative uptake of m-[123I]iodobenzylguanidine were detectable between patients and the control group. Only in two sectors of the basal anterolateral region P values < 0.01 were present. Thus, using m-[123I]iodobenzylguanidine scintigraphy as marker of cardiac adrenergic supply, no evidence of altered presynaptic hyperadrenergic supply was present in patients with mitral valve prolapse. These findings suggest postsynaptic regulation abnormalities to be preponderant in this condition.

3-Iodobenzylguanidine↗
PubMed1992

[Scintigraphic imaging of head and neck cancers with 99m technetium (v) dimercaptosuccinic acid. A prospective clinical study].

In patients with cervical metastases conventional examination by ultrasound, CT or MRI imaging often fails to identify an unknown primary tumor. Also the retrieval of a recurrent malignancy may be difficult. Scintigraphy, utilizing technetium-99m (v) dimercaptosuccinic acid was chosen for a prospective study in 17 patients to evaluate its properties for imaging metastasizing squamous cell carcinoma of the head and neck. Scintigraphic findings were correlated with the results of clinical examination and conventional imaging techniques. In all cases the primary tumor revealed good uptake of 99mTc(v)DMSA. Manifest cervical metastases could only be imaged in some cases. In future, therefore, 99mTc(v)DMSA scanning may be used for the detection of unknown primary tumors. However, it does not appear helpful in the evaluation of cervical nodes.

Carcinoma, Squamous Cell↗
PubMed1992

Kinetics of 99mTc-labelled antibodies against CD4 (T-helper) lymphocytes in man.

The availability of radiolabeled anti-CD4 antibodies permitted the study of their kinetic behaviour. Four patients suffering from rheumatoid arthritis were investigated prospectively. Three of them received 250 micrograms of 99mTc-labelled anti-CD4 antibody (MAX.16H5). One patient received in vitro 99mTc-antibody-labelled lymphocytes. 4% of the activity was excreted by the kidneys. From 4 to 24 h the splenic uptake decreased from 7.5 to 4%, the liver uptake increased from 25 to 30% the bone marrow uptake remained about the same 50% and the uptake of a single diseased joint (2%) increased slightly to 2.5%. 15 to 30 min after injection of the antibody a redistribution of labelled cells or antibody from liver and spleen to the circulating blood seemed to occur. The recovery rate (0-1 h) of in vivo labelled cells amounted to 30%, that of in vitro labelled cells to 19%. One patient was examined with in vitro labelled CD4-expressing lymphocytes. There was no difference in the antibody kinetics between in vitro and in vivo labelled cells. The authors suggest that circulating CD4-lymphocytes can be labelled with monoclonal antibodies. The kinetics of these in vitro labelled cells and the injected labelled antibody itself resembles that of recirculating lymphocytes.

Antibodies, Monoclonal↗
PubMed1992

Diagnostic accuracy of 99mTc-anti-CEA immunoscintigraphy in patients with liver metastases from colorectal carcinoma.

17 patients with 43 liver metastases from colorectal carcinoma were studied by immunoscintigraphy (IS) using a 99mTc-labelled monoclonal anti-CEA antibody (BW 431/26). Sensitivity and diagnostic accuracy were 21% for all liver lesions, but 47% considering the number of patients (at least one positive finding out of multiple metastases) and 77% in patients with a single metastasis. SPECT imaging did not improve sensitivity markedly in this series. There was no correlation with CEA serum levels. Liver metastases of intermediate size with moderate tumour necrosis seem to be favourable to IS. Major reason for the low sensitivity is the poor tumour-to-background ratio caused by high unspecific uptake of 99mTc-labelled antibodies in the RES of the liver. At the moment, IS seems be only a supplementary method to conventional diagnostic procedures.

Adenocarcinoma↗
PubMed1991

[Human anti-murine immunoglobulin antibodies as disturbing factors in TSH determination].

Monoclonal murine antibodies are increasingly used for immunotherapy and in vivo diagnostic procedures such as immunoscintigraphy. The therapeutic or diagnostic reagent however, is a foreign antigen, which may induce host reactivity. This may interfere with the therapeutic or diagnostic reagent in vivo, resulting in a loss of efficacy or the necessity to increase dosages. In addition, there is an important interference to in vitro immunoassays detecting specific antigens utilizing murine monoclonal antibodies. In the present study, sera of patients who had undergone a therapeutic trial using 140 mg of an anti-CD4 antibody, were investigated. Human anti-murine-immunoglobulin-antibodies (HAMA) were detected 2-3 weeks after treatment was started and reached maximal amounts of 0.8 micrograms/ml after a single and 2 micrograms/ml after a repeated treatment course. Parallely raised values of TSH were found in sera containing HAMAs of more than 0.3 micrograms/ml. Elevations of TSH levels up to 13 microU/ml were most pronounced after a repeated trial of the murine antibody and were detectable up to 20 weeks.

Antibodies, Monoclonal↗
PubMed1991

Octreotide scintigraphy localizes somatostatin receptor-positive islet cell carcinomas.

Tyr-3-Octreotide is a synthetic derivative of somatostatin and a somatostatin-receptor analogue. The iodine-123-labelled compound localizes somatostatin-receptor-positive tumours. In this paper two patients are reported in whom somatostatin receptors were demonstrated in vitro. In a 60-year-old female with an islet cell carcinoma of the pancreas, multiple liver metastases and previously unrecognized bone metastases in the right acetabulum could be diagnosed as the reason for a persistent hypoglycaemia. In a 60-year-old male an islet cell carcinoma of the pancreas was localized with 123I-Tyr-3-octreotide. The somatostatin receptors were demonstrated in vitro and the tumour was successfully treated with somatostatin. These studies demonstrate that 123I-Tyr-3-octreotide offers the possibility of localizing somatostatin-receptor-positive tumours and their metastases. Moreover the method makes it possible to determine the receptor status of a tumour in vivo.

Adenoma, Islet Cell↗
PubMed1991

[In-vitro-study and patient examinations with MRT: the significance of metal implants].

This study presents the results of in-vitro and clinical experiences with metallic implants during MRT investigations. In-vitro temperature measurements of various implants showed little temperature rise depending on the shape and the orientation in the static magnetic field (max. 0.3 degrees C). Ferromagnetic forces could not be detected with these implants. In contrast, severe temperature increase (9.4 degrees C) was observed with an intratracheal spiral tube. Tubes of this type should not be used in MR imaging to avoid the risk of burning. 105 MR examinations were performed in patients with metallic implants (CNS shunts, aortocoronary bypass grafts, aortic-, mitral-prosthesis, orthopedic implants, skin staples, shrapnels). Patients with vascular clips were accepted for MR imaging when the clips were non-ferromagnetic only. No adverse effects were observed in these patients.

Ferric Compounds↗
PubMed1991

Congenital myocardial sympathetic dysinnervation (CMSD)--a structural defect of idiopathic long QT syndrome.

Concerning the pathogenetic mechanism of idiopathic long QT syndrome (LQTS), the hypothesis of a specific sympathetic imbalance has gained general acceptance, but its validity has never been proven. To test this hypothesis I-123-MIBG, an analogue of norepinephrine and guanethidine, was used to provide scintigraphic display of the efferent cardiac sympathetic innervation. Twelve members of four LQTS families (mean age 38.2 +/- 17.2 years, eight males) and eight healthy volunteers (mean age 48.2 +/- 13.3 years, five males) were studied by means of I-123-MIBG single photon emission computed tomography (SPECT). A quantitative analysis of all scans was performed. All scans of the healthy volunteers show a uniform tracer uptake with sometimes slightly decreased activity in the apex. (1) All patients with QTc greater than 440 msec (n = 5); (2) all, who had suffered from at least one episode of torsade de pointes, ventricular fibrillation (VF) or syncope (n = 5); and (3) all symptomatic patients with QTc prolongation (n = 4) have reduced or abolished (P less than 0.02) MIBG uptakes in the inferior and inferior septal parts of the left ventricle (congenital myocardial sympathetic dysinnervation [CMSD]). Additionally, one female without symptoms or QTc prolongation (LQT) shows an abnormal MIBG SPECT similar to the one of her daughter, who has LQT and symptoms. One male without LQT, who had suffered from VF shows CMSD similar to his father, who has LQT, but no symptoms. All members of the families with normal MIBG SPECTs have neither LQT nor symptoms. In all families CMSD fulfills the criteria of autosomal-dominant inheritance. Normal QTc-interval predicted only in 57% normal cardiac sympathetic innervation in the present LQTS families. Therefore, quantitative I-123-MIBG SPECT enables to identify myocardial sympathetic dysinnervation as structural defect in LQTS. CMSD is associated with and without LQT and presents a pattern of autosomal-dominant inheritance. LQT at rest or during exercise was specific (100%), but less sensitive (63%) in the assessment of CMSD than I-123-MIBG SPECT.

3-Iodobenzylguanidine↗
PubMed1991

99mTc-labelled anti NCA-95 antibodies in prosthetic heart valve endocarditis.

A 54-y old women with earlier replacement of the mitral and aortic valves and clinical signs of localized endocarditis was studied with 99mTc-labelled anti NCA-95 antibody. Whereas echocardiographic findings were negative, increased radionuclide uptake was observed left parasternal over the mitral valve as a sign of prosthetic valve endocarditis. This result could be confirmed by a similar study with leukocytes labelled in vitro with 111In-oxine.

Antibodies, Monoclonal↗
PubMed1991

Biokinetics and estimation of dose from 99mTc-labelled polyclonal human immunoglobulin (HIG).

Recently, polyclonal unspecific human immunoglobulin was suggested as a new agent for the localization of inflammatory lesions. Little information about the biodistribution of this radiopharmaceutical was reported so far. To obtain further information, 99mTc-labelled human immunoglobulin (HIG) was administered to a volunteer with presumed normal biokinetics. The absorbed doses to the organs were calculated according to the MIRD concept. The scintigraphic images at 1, 2, 4 and 24 h post injection demonstrated a prolonged activity retention in the blood and high activity in the kidneys, bladder and also in the liver. No significant uptake in the bowels and the marrow could be observed over the whole period of study. 27.4% of the administered activity was excreted in the urine within 24 h. The calculated organ absorbed doses, all in microGy/MBq, were estimated as follows: whole body 2.7, liver 7.3, spleen 12.0, kidneys 15.3, lungs 3.2, marrow 9.6 and gonads 17.0. From these results an effective dose equivalent of 7.9 x 10(-3) mSv/MBq was calculated. The cancer risk estimate of 5 x 10(-5), using 370 MBq 99mTc-HIG, may be considered quite low in comparison to other scintigraphic methods of diagnosing inflammation.

Abdomen↗