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Biomedical subjects

F Wolf

Publications and source records attributed to F Wolf.

At least 55 records · Page 3Linked to original sources
PubMed1998

Generalized granuloma annulare and hepatitis B vaccination.

As hepatitis B vaccination is becoming generalized in Europe, cutaneous adverse events are being more frequently reported in the literature. We report the first case of generalized granuloma annulare following hepatitis B immunization. A 51-year-old woman presented a generalized granuloma annulare one month after the one-year booster injection of the hepatitis B vaccine. The lesions resolved with sulfone therapy. We observed an identical recurrence three weeks after the five-year booster.

Back↗
PubMed1998

Rat antigen-induced arthritis: cartilage alterations assessed with iodine-123-antileukoproteinase.

UNLABELLED: Imaging of cartilage alterations was attempted in joints of rats with chronic antigen-induced arthritis (AIA) using the cationic 123I-labeled serine proteinase inhibitor antileukoproteinase (123I-ALP; pI > 10), which selectively accumulates in normal cartilage, presumably through interaction with negatively charged proteoglycans. METHODS: Iodine-123-ALP or 123I-myoglobin, a control protein of comparable size but with different isoelectric point (pI=7.3) was injected intravenously into normal or AIA rats. Joint accumulation was followed by scintigraphy for 14 hr. Tissue radioactivity was assessed by well-counter measurements after dissection. The content of charged molecules in articular cartilage was determined by toluidine blue staining; the degree of joint destruction was assessed in parallel by x-ray, ex vivo MRI and histopathology. RESULTS: In intact articular cartilage, ALP accumulated to a significantly higher degree than myoglobin. This preferential accumulation was lost in rats with chronic AIA. The target-to-background ratio for 123I-ALP negatively correlated with the loss of toluidine blue staining in cartilage, which documents depletion of charged matrix molecules (r=-0.92, p < 0.01 at 4 hr; r=-0.97, p < 0.01 at 13 hr). ALP scintigraphy was sensitive in detecting cartilage alterations, even though the degree of joint destruction and inflammatory infiltration was mild, as demonstrated by x-ray, MRI and histopathology. CONCLUSION: In rat AIA, loss of ALP accumulation appears to document proteoglycan depletion in mildly altered arthritic cartilage. ALP scintigraphy may represent a functional assay for early, premorphological cartilage alterations in human arthritis as well.

Animals↗
PubMed1997

Myocardial damage assessed by indium-111-antimyosin: correlation with persistent enteroviral ribonucleic acid in dilated cardiomyopathy.

The persistence of enteroviral ribonucleic acid (RNA) in the myocardium has been implicated as a pathogenetic factor in idiopathic dilated cardiomyopathy. Enteroviral persistence may lead to myocardial cell membrane damage, resulting in increased uptake of antimyosin antibodies. To further evaluate this hypothesis, a direct comparison of myocardial antimyosin uptake with the presence of enteroviral RNA was performed in ten patients (one female, nine male; 53+/-8 years) with chronic dilated cardiomyopathy. Planar antimyosin images were obtained 48 h after the injection of indium-111-labelled antimyosin Fab. Using a region of interest technique, the heart to lung uptake ratio (HLR) was calculated as a semiquantitative parameter of myocardial tracer uptake. Cardiac catheterization was performed to assess left ventricular function and to obtain myocardial biopsy samples. In the biopsy samples, gene amplification by polymerase chain reaction (PCR) was used to specifically detect enteroviral RNA. In the ten patients, the left ventricular ejection fraction was 39%+/-11% and the end-diastolic volume 131+/-46 ml/m2. The HLR was 1.72+/-0.21 and showed no correlation with functional parameters. In two patients with a positive PCR consistent with persisting enteroviral RNA, the HLR was not higher than that in eight patients with a negative PCR (1.46+/-0. 18 vs 1.78+/-0.18, respectively). These results suggest that increased uptake of 111In-antimyosin in chronic idiopathic dilated cardiomyopathy cannot be explained by pure persistence of enteroviral RNA. Other pathogenetic factors such as myocardial autoantibodies or microvascular spasm may be responsible for myocyte membrane damage detected by antimyosin.

Antibodies, Monoclonal↗
PubMed1997

NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibody therapy.

The aim of this study was to investigate if dynamic gadolinium-DTPA-supported magnetic resonance (MR) imaging can monitor the therapeutic effect of a fast-acting immuno-modulating drug like anti-tumour necrosis factor alpha (anti-TNF-alpha) monoclonal antibody (moab) in patients with rheumatoid arthritis (RA). Dynamic MR imaging was performed on 64 joints in a total of 18 patients before and after infusion with either a placebo or 1 or 10 mg/kg of anti-TNF-alpha moab. Additionally, treating the placebo group and reinfusing the verum group with either 3 or 10 mg/kg was monitored by quantitative nuclear magnetic resonance (NMR). Time-dependent signal intensity changes were then correlated with a total of five Paulus criteria and with ESR and C-reactive protein (CRP). No changes in either the gadolinium uptake or clinical parameters were seen after the infusion of a placebo. Therapy with 1 mg/kg anti-TNF-alpha moab resulted in a significant decrease in clinical disease activity, as well as in gadolinium-DTPA uptake in dynamic NMR studies. However, correlations between singal intensity changes and Paulus criteria were only demonstrated for the variable "doctor's evaluation of disease activity". Patients given 10 mg/kg moab demonstrated a very significant improvement in all clinical manifestations of their disease, as well as a high significant reduction in gadolinium uptake (P = 0.004). In addition, the latter group showed significant correlations between time-dependent signal intensity changes and five Paulus criteria: "number of swollen joints", "number of painful joints", "duration of morning stiffness", "doctor's evaluation of disease activity" and "patient's evaluation of disease activity". No differences and correlations were seen for ESR and CRP. We concluded that dynamic NMR studies are suitable to monitor inflammatory activity in RA patients under therapy with biological response modifiers such as anti-TNF-alpha moab.

Adult↗
PubMed1997

Distribution of radiolabelled anti-CA125 monoclonal antibody OC125-F(ab)2-fragment following resection guided by antibodies (REGAJ) in ovarian cancer patients.

Ovarian cancer is a highly malignant tumor of mainly postmenopausal women. The long-term prognosis of this malignancy is largely determined by micrometastasis present at the time of second-look surgery. In general, patients face a poor outcome. New radio-immunoscintigraphic methods to target tumor tissue specifically via antigen-antibody binding were developed. However, few studies so far investigated the pattern of in vivo distribution of radiolabelled mAbs and/ or the specificity of antigen-antibody interaction. In this study we examined the immunological interaction and distribution of 131l-OC125-F(ab')2-fragment, an anti-CA-125 mAb, in patients with CA-125 positive ovarian malignancies. Sixteen patients with primarily CA-125 positive gynecological tumors underwent REGAJ surgery. Biopsies of tumor tissue and not tumor infiltrated tissue, serum, and ascites were sampled during or prior to REGAJ surgery, respectively. After preparation of tissue cytosols, samples were assessed for CA-125 and radioactive uptake. By radiochromatography immunological analysis for presence of the target antigen CA-125, the mAb 131l-OC125-F(ab')2-fragment, and immune complexes was performed on different specimen. CA-125 concentrations were higher in serum samples, ascites, and malignant tissue biopsies of malignoma patients compared to those without signs of malignant disease. CA-125 was higher in the tissue cytosol than in the cell membrane fraction. Gel filtration revealed CA-125 with moieties of 75,000 to > 600,000 d. Accumulation of radioactivity was more frequently associated with the presence of unbound 131l-OC125-F(ab')2-fragment or high molecular weight immune complexes. Radioactive uptake, however, was not confined to tissue of high CA-125 expression. Moreover, both immune complex as well as 131l-OC125-F(ab')2-fragment could be isolated from cytosols of tissue not infiltrated by tumor cells as well. Our study demonstrates that the majority of CA-125 is located intracellularly and thus inaccessible to 131l-OC125-F(ab')2-fragment per se. The uptake of 131l-OC125-F(ab')2-fragment into the cytosol of tumor-free and malignant tissue samples prompts us to speculate that certain mechanisms for antigen-specific and nonspecific cellular trafficking of mAbs do exist. We present a model to explain our observations.

Antibodies, Monoclonal↗
PubMed1997

The serine proteinase inhibitor antileukoproteinase specifically accumulates in normal but not in arthritic cartilage.

OBJECTIVE: To investigate whether the serine proteinase inhibitor antileukoproteinase (aLP) specifically accumulates in articular and extraarticular cartilage in normal and arthritic rats after intravenous (i.v.) injection. METHODS: [123I] or [125I] radiolabeled aLP and a control protein of comparable size were injected iv into normal rats or rats with chronic, antigen induced arthritis (AIA). Joint accumulation of the 2 proteins was followed by scintigraphy and organ tissue radioactivity was assessed by autoradiography and well counter measurements. Immunoprecipitation of aLP from articular cartilage was also performed and the content of charged molecules in normal and arthritic cartilage determined using toluidine blue staining. RESULTS: The accumulation of both radiolabeled aLP and control protein in the normal joint was clearly detectable by scintigraphy, with significant differences between the 2 proteins. In accordance with the scintigraphic data, direct tissue radioactivity measurements, immunoprecipitation, and autoradiography showed highly specific accumulation of radiolabeled aLP in articular and extraarticular cartilage of normal rats. The specific accumulation of aLP in articular cartilage was lost in rats with AIA in parallel with a loss of charged matrix molecules. CONCLUSION: I.v. injected serine protease inhibitor aLP specifically accumulates in articular and extraarticular cartilage of normal rats. This physiological pathway of cartilage accumulation, lost in proteoglycan depleted arthritic cartilage, may serve to maintain the local balance between proteinase function and inhibition.

Animals↗
PubMed1997

Anticardiolipin antibodies are not associated with restenosis or endothelial activation after percutaneous transluminal angioplasty.

OBJECTIVE: Restenosis following percutaneous transluminal angioplasty (PTA) continues to be a major clinical problem. Anticardiolipin antibodies (aCL) have been established as risk factors for venous or arterial thrombosis. The aim of this study was to assess: a) the influence of positive aCL upon restenosis within 6 months after PTA, b) the possibility of a seroconversion from negative to positive aCL after PTA and c) a possible link between positive aCL and endothelial activation. EXPERIMENTAL DESIGN: 71 patients (50 men and 21 women, age 68+/-13 years) with peripheral arterial occlusive disease (PAOD, Fontaine II-IV) undergoing a successful PTA entered the study and were prospectively followed for 3 and 6 months thereafter. INTERVENTIONS: PTA was carried out successfully and noninvasive grading was done with duplex scanning. Laboratory investigation included aCL, thrombin generation markers, such as thrombin-antithrombin III complexes and prothrombin fragments 1+2, as well as thrombomodulin, soluble P-selectin, E-selectin and the vascular cell adhesion molecule-1, as endothelial activation markers. RESULTS: 30/71 (42.3%) patients developed restenosis (>50% reduction of the lumen diameter) within 6 months after PTA. 9/71(12.7%), had positive aCL IgG (19-35 GPL) and/or IgM (14-103 MPL) at all three measurements. 2/9 (22.2%) of aCL positive and 28/62 (45.2%) of aCL negative patients had restenosis at 6 months after PTA (relative risk RR=0.51, 95%-Cl: 0.14-1.78, chi2 non-significant). All other parameters did not differ between aCL positive and -negative groups. CONCLUSIONS: Our findings suggest that: a) patients with PAOD have a slightly higher prevalence of positive aCL compared to the general population, but no association is evident between positive aCL and restenosis within 6 months after PTA, b) no seroconversion from negative to positive aCL occurred within 6 months after PTA, c) no association of aCL with endothelial activation markers or thrombin generation markers was found.

Aged↗
PubMed1997

Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion.

AIM: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. METHODS: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. RESULTS: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. CONCLUSION: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and color-coded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion.

Adult↗
PubMed1997

An expanded neonatal morbidity scale for premature infants.

We revised a neonatal morbidity scale (the NMS) that has served as a means for comparison of neonatal illness in studies of high-risk neonates after initial hospital discharge. With an inception cohort approach, 89 premature infants at an urban university hospital were studied with the expanded scale (the ENMS). The original scale, published in 1983, was reworked and expanded based on advances in the diagnosis and management of neonates. A social risk scale was added. Linear and logistic regression analyses were used to judge validity of the newly revised scale and to examine its predictive ability for outcomes at six months of age. Concurrent validity was supported by the relationship between the ENMS-SRS and: birthweight (R2 = .54), gestational age (R2 = .50), length of stay (R2 = .47). Inter-rater reliability was .95. The ENMS, embodying a contemporary patient profile, is valid for a population of premature infants in a U.S. urban setting and has predictive validity for a few outcomes within six months of discharge from a special care unit.

Female↗
PubMed1996

99m-Tc-HMPAO-SPECT in diagnosis of early cerebral vasculitis.

The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's syndrome. Of these, 18 patients showed overt neuropsychiatric symptoms, so-called major symptoms (e.g. motoric or sensible defects); 6 had mild symptoms like headache or cognitive disorders, so-called minor symptoms: 16 patients did not present with any of these symptoms. SPECT abnormalities were detected in 16 of the 18 patients with overt neuropsychiatric symptoms (89%). Five of the 6 patients with minor symptoms (83%) and 5 of the 16 patients without neurological symptoms (31%) also had SPECT abnormalities. There was no relation to disease activity or duration. We concluded that the high sensitivity of SPECT (87.5%) in detecting perfusion abnormalities among the evaluated group of patients indicates its suitability for early diagnosis of vasculitic CNS involvement.

Adult↗
PubMed1996

Rapid imaging of infections with a monoclonal antibody fragment (LeukoScan).

The diagnostic accuracy for imaging infection with a technetium-99m-labeled antigranulocyte Fab' fragment (LeukoScan) was prospectively examined in a multicenter study. Scintigraphy was performed in 53 patients at 1 to 6 hours and at 24 hours after injection of the labeled antibody fragment. Thirty-nine sites of infection were detected and confirmed by histologic study, cytologic study, other imaging procedures, or by followup. Thirty-eight of the 53 patients also were studied with technetium-99m-Exametazim or indium-111-oxine labeled leukocytes within 1 week of the LeukoScan study. In 21 patients with 25 osteomyelitic lesions, LeukoScan recognized 13 of the lesions as being true positive ones, 10 as being true negative ones, and 2 as being false negative ones, whereas the leukocyte scan showed 9 true positive results, 5 true negative results, and 2 false negative ones. Sensitivity specificity, and diagnostic accuracy of LeukoScan were 90.0 %, 84.6 %, and 87.9 %; and with autologous leukocyte scintigraphy were 83.9%, 76.5%, and 81.3%, respectively. The sensitivity of LeukoScan was independent of the amount of the labeled antibody injected (0.1 - < 0.5 mg, 96.2%; 0.5 - < 0.9 mg, 80.0%; 0.9 - 1.0 mg, 77.8%). False positive lesions were detected in a periprosthetic calcification, a frontal hyperostosis, and 2 periprosthetic hips that had loosened. Human antimouse antibody could not be detected in any of the 13 patients tested 1 or 3 months after injection. LeukoScan is suitable for imaging infectious lesions and may have diagnostic advantages compared with autologous leukocyte scintigraphy.

Adult↗
PubMed1995

Targeting of liver metastases of colorectal cancer with IgG, F(ab')2, and Fab' anti-carcinoembryonic antigen antibodies labeled with 99mTc: the role of metabolism and kinetics.

The aim of this study was to investigate targeting of the liver metastases by directly 99mTc-labeled complete (IgG) and fragmented antibodies [F(ab')2 and Fab'] in relation to their kinetics and metabolic fate. A total of 127 patients with metastatic colorectal cancer were examined [IgG1, BW 431/26 (Behringwerke, Marburg, Germany) n = 50; F(ab')2, F023C5 (Sorin Biomedica, Saluggia, Italy) n = 58; Fab', IMMU-4 (Immunomedics, Morris Plains, NJ) n = 19]. Native monoclonal antibodies (MAbs), serum samples from 10 min to 24 h postinjection (p.i.), and urine were analyzed by gel filtration chromatography. Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 min to 24 h p.i. (region-of-interest technique). In BW 431/26, 96% of injected activity was labeled IgG1; in F023C5, 29% was F(ab')2, and 71% was Fab'; and in IMMU-4, 92% was Fab', and 8% was F(ab')2. Serum half-lives were: IgG1, 36 h (liver uptake predominant); F(ab')2, 16 h; and Fab', 4 h (renal uptake predominant). All MAbs were metabolized, fragments more rapidly than IgG, to low-molecular-weight products and excreted into the urine (e.g., Tc-cystine). In targeting liver metastases, sensitivities were found to be higher for fragments (44.1, 72.5, and 80% for BW 431/26, F023C5, and IMMU-4, respectively) but at significantly lower tumor:background ratios than with IgG (1.78 +/- 0.29 versus 1.29 +/- 0.11 and 1.43 +/- 0.53; P < 0.01). With IgG, there was a continuous tumor uptake over 24 h, whereas with fragments, the maximal uptake occurred mostly within 1 h, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4 h with fragments but often not before 24 h with IgG. These results show that the higher sensitivity of fragments in liver lesion targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact MAbs show a slow, continuous uptake, leading to higher tumor:background ratios at later p.i. times, often beyond the imaging possibilities of 99mTc.

Carcinoembryonic Antigen↗