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Biomedical subjects

F Wolf

Publications and source records attributed to F Wolf.

At least 73 records · Page 4Linked to original sources

Anticardiolipin antibodies do not seem to be associated with APC resistance in vivo or in vitro.

Anticardiolipin antibodies (aCL) or lupus anticoagulants (LA) have been found to exert an inhibitory action upon the activation and function of protein C, a natural coagulation inhibitor. Recently an in vitro phenomenon called resistance to activated protein C (APC resistance) has been described as the most frequent cause of hereditary thrombophilia. In order to see whether a positive association of APC resistance with aCL exists we examined plasma of 162 consecutive outpatients referred for thrombophilia screening. Further, the IgG fraction was isolated from plasma of two aCL-positive and LA-negative patients and of two aCL-negative healthy subjects by means of protein A affinity chromatography. Each of these isolates was mixed with normal plasma, and the APC resistance was assayed; 25/162 (15.4%) patients had confirmed abnormal APC resistance. Only 1/25 (4.0%) APC resistance-positive patients and 11/137 (8.0%) APC resistance-negative patients had positive IgG- and/or IgM-aCL (p = 0.5, nonsignificant). In the in vitro test system the APC resistance ratio remained unaffected after addition of normal IgG or aCL-IgG fraction in the tested normal plasma and did not deviate from the range of buffer controls. These data do not suggest any association of aCL with abnormal APC resistance. aCL-IgG fractions from aCL-positive and LA-negative plasmas do not interfere with the APC resistance test system in vitro in low concentration.

Adolescent↗

Impaired nasal mucociliary clearance in long-distance runners.

For years physicians have observed a high incidence of upper respiratory tract infections (URTI) after strenuous exercise. Mucosal surfaces represent a first-line-of-defense against infections, and pollutants or organisms entrapped in respiratory secretions are cleared by mucociliary transport. Little is known about this mechanism during exercise. The purpose of this study was to examine the nasal mucociliary clearance (MMCC) in amateur runners competing in a marathon race. Twelve amateur runners entered in an inner-city marathon race and 10 healthy sedentary subjects participated in the study. On the day of the race the outside temperature was 3 degrees C. Nasal mucociliary transit time (NMTT) was measured daily for 1 week before and 1 week after the race by the saccharin sodium/indigo carmine method. Nasal tissue biopsies were taken, and cilia beat frequency (CBF) was measured as viability and function of ciliated epithelial cells were determined. NMTT was significantly prolonged after the race (17.1 +/- 1.2 min vs 8.9 +/- 0.9 min; athletes vs control group; mean +/- SEM) and returned to baseline over several days. CBF was significantly reduced only in the first 24 hours after the race (7.31 +/- 0.65 Hz for athletes vs 9.94 +/- 0.45 Hz, controls. After the race, athletes showed a higher percentage of ciliated cells with immotile cilia (37.1 +/- 1.3% vs 27.8 +/- 1.1%, athletes vs controls) or dead ciliated cells (7.3 +/- 0.9% vs 4.1 +/- 0.8%). The findings suggest impairment of NMCC up to several days after strenuous exercise, which might be partially caused by abnormally functioning ciliated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Is there still a need for Tc-99m DMSA renal imaging?

Scintigraphy with Tc-99m MAG3 is, to date, the most commonly used technique for evaluating separate renal function (SRF). In this study, the performance of this technique is compared to Tc-99m DMSA. A total of 37 patients with various kidney disorders (12 children and 25 adults) underwent both Tc-99m DMSA and Tc-99m MAG 3 scintigraphy. In children and adults of normal weight the correlation coefficient between the two methods was 0.99 (P < 0.001), whereas in individuals who were more than 10% overweight according to Broca, or who had abnormal anatomical positions of the kidneys, the correlation coefficient was 0.82 (P < 0.05). Scintigraphy with Tc-99m DMSA was more accurate in renal parenchyma lesions. These results indicate that Tc-99m DMSA scintigraphy is preferable for the evaluation of SRF in patients who are more than 10% overweight, or have abnormal positions of the kidneys.

Adolescent↗

Somatostatin receptor expression in the thyroid demonstrated with 111In-octreotide scintigraphy.

Neuroendocrine tumors with somatostatin receptor expression may be localized by 111In-octreotide scintigraphy. This study examines those thyroid conditions where 111In-octreotide uptake could be observed also in the thyroid gland. 26 consecutive patients who underwent 111In-octreotide scintigraphy for tumor localization were additionally examined for thyroid disease by sonography and 99mTc-pertechnetate scintigraphy. 12 of these patients had no significant thyroid uptake and had an euthyroid normal-sized thyroid gland 14 patients with 111In thyroid uptakes had endemic goiters, two of them with thyroid autonomy and one with Graves' disease. Thus, 111In-octreotide thyroid uptake was predominantly seen in patients with endemic goiter with or without thyroid autonomy.

Adult↗

Rat adjuvant arthritis: imaging with technetium-99m-anti-CD4 Fab' fragments.

UNLABELLED: The abundance of CD4 molecules on inflammatory cells in the synovial membrane renders anti-CD4 monoclonal antibodies (MAbs) or their fragments very promising for specific imaging of arthritic joints. METHODS: Joint uptake and body distribution of a 99mTc-labeled Fab', derived from the anti-rat CD4 MAb W3/25 (IgG1), were investigated following intravenous injection in normal and adjuvant arthritic rats. An isotype-matched Fab' (anti-human nonspecific crossreacting antigen-90) was used as control. RESULTS: A 14-hr sequential pinhole scan of the ankle joints revealed that both the anti-CD4 and the control Fab' accumulated to a higher degree in arthritic than in normal ankle joints; however, accumulation of the anti-CD4 Fab' in arthritic joints exceeded that of the control Fab' (approximate to 1.6 fold). Preferential joint accumulation of anti-CD4 Fab' was confirmed by whole-body scans at 14 hr and by direct well counter measurements of tissue samples at 16 hr following injection. Unlike the control Fab', the anti-CD4 Fab' preferentially accumulated in the liver and lymph nodes, organs rich in CD4-positive cells, as observed by direct tissue measurements. CONCLUSION: Despite its monovalency, the anti-CD4 Fab' retains the in vivo selectivity for CD4-positive cell-rich tissues, previously reported for the complete anti-CD4 MAb, and improves imaging of inflamed joints in experimental adjuvant arthritis.

Animals↗

99mTc-trimethyl-BrIDA scintigraphy in HIV-related cholangiopathy.

A HIV-infected 37-year-old man with diffuse mid-abdominal pain and elevated liver enzymes was sequentially studied by sonography, computed tomography (CT), 99mTc-trimethyl-BrIDA scintigraphy and endoscopic retrograde cholangiopancreatography (ERCP). CT and sonography did not lead to a final diagnosis. Cholescintigraphy showed signs of cholecystitis and sclerosing cholangitis with intra- and extrahepatic bile duct dilatation. These findings could be confirmed by ERCP, rendering HIV-associated cholepathy probable. Cytomegalovirus infection was demonstrated by polymerase chain reaction from bile fluid and the presence of cryptosporidia infection in a histology specimen isolated by ERCP. Therefore, biliary scintigraphy seems promising for screening for HIV-associated cholangio- and cholecystopathy, being less invasive and less bothering for the patient than ERCP.

Adult↗

[Neonatal hyperthyroidism in non-diagnosed Basedow's disease of the mother. Problems of diagnosis and therapy illustrated by a case history].

A male preterm infant (born at 34 weeks, birth weight 2130 g) developed jaundice (total bilirubin 7.4 mg/dl), hepatosplenomegaly, thrombocytopenia (82,000/microliters) and a raised C-reactive protein (1.2 mg/dl). Although sepsis was suspected, no organism was demonstrated. When the mother visited the child for the first time after 2 weeks, she had florid hyperthyroidism. This explained many of the child's clinical features (poor weight gain, tachycardia, exophthalmos). Both mother and child had raised TSH receptor antibodies (mother: 684.6 U/l; 54.1 U/l, normal < 15 U/l), an increased free T4 and a suppressed TSH. Because of the tachycardia, the child was treated with propranolol (1 mg/kg.d for 5 weeks). He was also initially given Lugol's solution (25 mg iodide/kg.d for 1 week) and then propylthiouracil (7 mg/kg.d) because of the increasing total T3. L-Thyroxine replacement was subsequently required for a period of 2.5 weeks because of treatment-related hypothyroidism. Since stopping treatment (at 12 weeks of age), the child has developed normally.--Neonatal hyperthyroidism due to transplacental transfer of TSH receptor antibodies associated with maternal Graves' disease is a rare self-limiting condition. However, it may pose considerable danger to the child both in utero and postnatally (with a mortality if untreated of up to 20%). Interdisciplinary cooperation is essential.

Adult↗

Imaging rheumatoid arthritis joints with technetium-99m labelled specific anti-CD4- and non-specific monoclonal antibodies.

A direct comparison of the joint-imaging properties of inflammation-specific- and non-specific monoclonal antibodies (Mabs) was possible in a patient suffering from long-standing, severe rheumatoid arthritis (RA). This patient received an anti-CD4- and an anticarcinoembryonic antigen (anti-CEA) Mab, both labelled with technetium-99m, 9 days apart from each other. The anti-CD4 Mab was superior to the isotype-matched anti-CEA Mab in imaging inflamed joints. In the knee joint, the target-to-background ratio of the synovial membrane (SM) activity in comparison to that of adjacent large vessels was 1.22 (SM/muscle 1.55) for the anti-CD4 Mab and 0.53 (SM/muscle 0.92) for the anti-CEA Mab, in both cases 4 h after injection of the immunoglobulin. Since the CD4 antigen is present on the surface of T-helper lymphocytes and macrophages infiltrating the inflamed synovial membrane, imaging with the anti-CD4 Mab may allow more specific detection of inflammatory infiltrates in RA.

Aged↗

Formation of field discontinuities and islands in visual cortical maps.

The representations of visual hemifields in the extrastriate areas of various species exhibit field discontinuities and islands. We propose that these violations of retinotopy are a developmental consequence of the elongated shape of the respective cortical areas. To substantiate this claim, we investigated a model of activity-driven map formation. In agreement with observations, this model yields maps with field discontinuities if the cortical areas exceed a threshold elongation. Moreover, within the same model island representations in the periphery and the area centralis can also be understood. A multistability of the solutions in the model gives a very simple explanation for the observed interindividual variability of maps in cats. The model leads to a prediction of the radial dependence of the areal magnification factor near field discontinuities, which could be accessible for a high precision mapping experiment.

Animals↗

Investigation of parasympathetic and sympathetic cardiac innervation in diabetic neuropathy: heart rate variation versus meta-iodo-benzylguanidine measured by single photon emission computed tomography.

In diabetic neuropathy disturbed autonomic cardiac innervation is associated with shortened life expectancy. Sympathetic dysfunction is likely to play a role in cases of cardiac death. The quantitative uptake of the radiopharmaceutical iodine-123-meta-iodo-benzylguanidine (MIBG) can be measured by single photon emission computed tomography (SPECT). It is an index of the functional integrity of sympathetic neurones in the heart. The respiratory heart rate variation--as assessed by a computerized device--reflects mainly parasympathetic cardiac innervation. In 25 diabetic patients and 19 healthy subjects MIBG-SPECT and heart rate variation tests were carried out. MIBG scans in all normal subjects showed homogeneous uptake of activity. In 12 out of 25 patients at least two heart rate variation tests were abnormal. MIBG-SPECT was more sensitive (abnormal in 17 out of 25). The lack of correlation between MIBG-SPECT results and spectral analysis of heart rate variation suggest that spectral analysis alone should not be regarded as an indicator of sympathetic cardiac innervation.

3-Iodobenzylguanidine↗

The use of monoclonal antibodies and antibody fragments in the imaging of infectious lesions.

The advantage of immunoscintigraphy over autologous leukocyte techniques in the imaging of infection is the simplicity of its use compared with techniques that require the isolation of autologous white blood cells. The advantage over 99mTc- or 111In-labeled nonspecific human immunoglobulin is the excellent target-to-background ratio, which results from an endogenous background subtraction with the whole antigranulocyte antibody (99mTc-anti-NCA-95; BW250/183) and a rapid clearance of the antibody using an antigranulocyte Fab'-fragment (99mTc-anti-NCA-90; IMMU-MN3). The whole antibody is helpful for imaging of soft tissue infections, peripheral bone, and abdominal infections. Problems may arise occasionally in regions with normal bone marrow that are caused by human antimouse antibody (HAMA) formation. An infection or the entire extent of inflammation can be proven or excluded only at 24 hours postinjection. In contrast, antigranulocyte Fab'-fragment may have its advantage in an earlier localization of infectious lesions (1 hour) owing to its smaller molecular size and its lower affinity for its epitope. This may be promising in the detection of spinal infections and in infections in regions with the presence of normal bone marrow. Also advantageous is the negligible HAMA response rate. Problems may arise in abdominal infections because of an intestinal excretion of activity as early as 4 hours postinjection in some cases but more usually at 24 hours.

Abdomen↗

Structural modifications of monoclonal antibodies following direct versus indirect labelling with 99Tcm: does fragmentation really occur?

In this study, the influence of direct and indirect 99Tcm-labelling on the molecular structural integrity of monoclonal antibodies and other immunoglobulin preparations was investigated. Molecular composition of antibody preparations [two IgG monoclonal antibodies, one F(ab')2 fragment (all directly labelled), one indirectly labelled polyclonal human immunoglobulin preparation] and of serum samples after antibody injection were studied using polyacrylamide gel electrophoresis (PAGE; non-reducing and reducing conditions) and gel filtration chromatography. With PAGE, depending on the conditions used, a variety of lower molecular weight products could be detected. When analysing the same antibody preparations by gel filtration chromatography, all complete antibody preparations appeared as homogenous proteins of IgG molecular weight (150 kD). In F(ab')2 fragments, some further fragmentation to Fab' was noticed. Neither in vitro nor in vivo (serum) evidence of smaller fragments could be detected by gel filtration, despite their presence in PAGE. We therefore conclude that through the reductive step of direct 99Tcm-labelling, interchain disulphide linkages are broken but the polypeptide chains of complete IgG remain associated by non-covalent linkages, whereas (F(ab')2 is fragmented further to form essentially Fab'. The protein-denaturating conditions of PAGE (even if performed non-reducingly) seem to produce artifacts, not representing the real in vivo condition. PAGE results should therefore be interpreted only with great care.

Antibodies, Monoclonal↗

Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT.

Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P = 0.002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences.

AIDS-Related Opportunistic Infections↗

[Somatostatin receptor scintigraphy in neuroendocrine tumors exemplified by a patient with hepatic metastases of gastrinoma].

In a 66-year old woman, who suffered from recurrent melena, diarrhea and hematemesis with multiple untreatable gastric and duodenal ulcers, a markedly increased basal and secretin-stimulated gastrin level, clinically a Zollinger-Ellison syndrome was assumed. The conventional diagnostic procedures (esophago-gastro-duodenoscopy, colonoscopy, endosonography, ERCP, abdominal CT and small bowel enema) had failed to reveal the localisation of any gastrinoma. The thereupon performed scintigraphy with In-111-pentetreotide showed four somatostatin receptor expressing liver lesions: two of them could be detected at first site in the consecutively performed MR scans, another retrospectively bearing in mind the scintigraphic images. Today, the somatostatin receptor imaging seems to be a highly sensitive procedure for detecting and localizing hormonally active gastroenteropancreatic tumors. At the same time it is a method for in vivo evaluation of the somatostatin receptor status of localized GEP tumors, thus delivering a decisive diagnostic step for the evaluation of the effectiveness of a therapy with somatostatin analogues before such an expensive therapy is started.

Aged↗

Detection of soft-tissue infections and osteomyelitis using a technetium-99m-labeled anti-granulocyte monoclonal antibody fragment.

UNLABELLED: Imaging of osteomyelitis and soft-tissue infections can be problematic with currently available agents; bone scans are often false-positive. Indium-111-oxine and 99mTc-HMPAO white blood cell (WBC) scans require ex vivo handling of blood with potential exposure to infectious agents, and 99mTc-antigranulocyte (IgG1) antibodies need 24 hr for final diagnosis. METHODS: We investigated the use of 99mTc-murine anti-granulocyte monoclonal Fab' fragment in 20 patients with suspected osteomyelitis of soft-tissue infections. All patients also had 99mTc bone scans and 111In-oxine or 99mTc-HMPAO white blood cell scans. The final diagnosis was confirmed by culture, biopsy, surgery, follow-up, x-rays, CT or MRI. In vitro studies performed on granulocytes demonstrated no effect on their function when the anti-granulocyte monoclonal antibody fragment was added. RESULTS: Sensitivity, specificity and diagnostic accuracy to detect infection was 88%, 75% and 80%, respectively. All lesions could be detected as early as 1 hr after injection of the antibody fragment. In comparison, WBC scanning had values of 86%, 78% and 81%, respectively. Some lesions could only be detected 24 hr following the injection of labeled WBCs. LeukoScan had three false-positives and WBC scanning had two false-positives. CONCLUSIONS: Immunoscintigraphy with 99mTc-NCA-90 Fab' fragments offers rapid localization of foci, rapid and simple use, a negligible HAMA response rate, no effect on granulocyte function and an accuracy comparable to WBC scanning.

Adult↗

Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus.

OBJECTIVE: Single-photon-emission computed tomography (SPECT) scanning was used to detect potential central nervous system (CNS) involvement in patients with systemic lupus erythematosus (SLE), by determining cerebral blood flow abnormalities. METHODS: SPECT scans were performed on 35 SLE patients, grouped into 3 categories: those without neuropsychiatric symptoms (n = 10), those with definite neurologic or psychiatric disorders (n = 10), and those with mild symptoms such as headache or memory disturbances (n = 15). SPECT scan features were classified as normal or as focal or diffuse defects in uptake. RESULTS: SPECT findings were normal in 9 of the 10 patients without CNS symptoms, and abnormal in 9 of the 10 patients with overt neuropsychiatric disease (with motor or sensory deficits). Interestingly, only 4 of the 15 patients (26.7%) with mild symptoms suggestive of CNS disease had normal SPECT findings; the 11 remaining patients showed focal (53.3%) or diffuse (20%) uptake defects. An association between SPECT findings and disease duration was also observed, but there was no correlation of SPECT results with overall disease activity, serologic findings, or medications used. CONCLUSION: Our data suggest that in a substantial proportion of patients, SPECT analysis may provide additional information on potential CNS involvement, and may therefore be useful in therapeutic decision-making and disease monitoring in order to prevent CNS damage.

Adult↗