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Biomedical subjects

F Wolf

Publications and source records attributed to F Wolf.

At least 19 recordsLinked to original sources

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

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

[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

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

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

[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

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

[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

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

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

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

Regional cerebral blood flow during focal seizures of temporal and frontocentral onset.

Ictal single photon emission computed tomography recordings were performed in 9 patients in the course of 11 seizures. Injections of radionuclide were made an average of 72 seconds after the onset of the seizure as indicated by electroencephalography. All patients also underwent interictal recordings. In 6 patients, the localization of the electroencephalographic focus and the morphological lesions corresponded with the ictal hyperperfusion. This could be seen in single photon emission computed tomography. Seizures triggered by hyperventilation, and seizures of patients with anatomical brain lesions (e.g., cysts, surgical defects, and recent injections of technetium-hexamethylene-propylene-amine-oxime) showed an absent or noncorresponding localization of the ictal recording. The ictal and interictal recording seems suitable as a confirmatory noninvasive method for the localization of the epileptogenic focus, particularly in the preoperative evaluation of epilepsy.

Adolescent

Imaging rheumatoid arthritis specifically with technetium 99m CD4-specific (T-helper lymphocytes) antibodies.

CD4 expressing T-lymphocytes are involved in the pathogenesis of rheumatoid arthritis, so the possibility of using radiolabelled CD4-specific antibodies to localise diseased joints was studied. Prospectively six patients with rheumatoid arthritis were investigated. Five of them received 200-300 micrograms of a 555 MBq technetium 99m CD4-specific antibody (MAX.16H5) and were examined with three phase bone scans. Max.16H5 (IgG1) was labelled according to the mercaptoethanol (Schwarz) method. Lymphocytes of one patient were isolated on a Ficoll-Hypaque gradient and labelled with the antibody in vitro. Scans were performed 1.5 h, 4 and 24 h post injection in anterior and posterior views. In all patients, diseased joints could be clearly imaged at as early as 1.5 h. The localisation of the diseased joints correlated (P less than 0.01) with the clinical signs, with the early methylene diphosphonate (MDP) scan (P less than 0.01) and only weakly with the late bone scan (P greater than 0.05). According to these data we conclude that 99mTc-labelled CD4-specific antibodies specifically image actively diseased joints in rheumatoid arthritis.

Antibodies, Monoclonal

Bone scan and red blood cell scan in a patient with epidermal naevus syndrome.

A bone scan and red blood cell scan in the rare epidermal naevus syndrome, associated with multiple haemangiomas of the bone and hypophosphataemic osteomalacia in a 20-year-old man are reported. The typical pattern of osteomalacia on the bone scan was associated with lesions of increased bone metabolism in the peripheral bones. The haemangiomas did not pool labelled red blood cells. Thus, the bone scan seems to be suitable for diagnosing the complete extent of haemangiomas in bone, but they could not be specifically proven by red blood cell pooling.

Adult