Visualizing inflammation activity in rheumatoid arthritis with Tc-99 m anti-CD4-mAb fragment scintigraphy.

PURPOSE: T-cell-located CD4 antigen represents one of the therapeutic targets in rheumatoid arthritis (RA). However, up to now there is no established imaging tool to visualize this target in vivo. The aim of our study was to assess the safety and tolerability of a technetium-99m labelled murine anti-human CD4 IgG1-Fab fragment ([(99m)Tc]-anti-CD4-Fab, [(99m)Tc]-EP1645) in patients with active synovitis due to RA, and to evaluate its potential as a marker of disease activity. METHODS: In the present phase I proof of principle study five patients with RA were examined. Planar scans of the whole body, hands, and feet were taken 30 min up to 24h after application of 550 ± 150 MBq [(99m)Tc]-anti-CD4-Fab, followed by visual analyses, comparison with clinical data in 68 joints per patient and semiquantitative analysis of hand and wrist joints. RESULTS: Neither infusion related adverse events nor adverse events during follow up were observed. No increase in human anti-murine antibody titres was seen. All patients had positive scans in almost 70% of clinically affected joints. Positive scans were also found in 8% of joints without evidence of swelling or tenderness. CONCLUSION: Scintigraphy with [(99m)Tc]-anti-CD4-Fab is a promising technique for evaluation of inflammatory activity in patients with RA, pre-therapeutical evaluation of CD4 status and therapy control. Tracer uptake in clinically inconspicuous joints strongly indicates diagnostic potential of [(99m)Tc]-anti-CD4-Fab. Whether this technique is eligible as a prognostic factor in RA needs to be analysed in further studies as well as the pathophysiological background of clinically affected joints lacking tracer uptake.

Smart textiles: a new drug delivery system for symptomatic treatment of a common cold.

Smart textiles provide the possibility of being coated with cineole, menthol, and camphor. Due to over-the-counter availability, ethereal oils are frequently used to treat a common cold. The existing pharmaceutical forms entail the risk of oral ingestion by children, which can cause severe intoxications. This risk could be limited by a smart textile application. Prior to applicability tests in children, the principal traceability of smart textile-applied ethereal oils at their site of action in the alveoli has to be demonstrated. Therefore, a crossover trial (ointment vs smart textiles) with 6 healthy volunteers was carried out as a proof-of-concept study. As a result, the principle proof is given that smart textile-applied ethereal oils are available at their site of action. Because of the volatility of the active ingredients, a close-fitting textile form has to be developed for further clinical development of smart textiles to achieve higher concentrations in the alveoli. Slower liberation properties and a more convenient skin sensation in comparison to available pharmaceutical forms may provide advantages for the applicability in both children and adults.

[Pain drawings of patients with orofacial pain. Comparison of acceptance and gain of information]. / Schemata zur Schmerzeinzeichnung bei Patienten mit orofazialen Schmerzen. Vergleich von Akzeptanz und Informationsgehalt.

AIM OF THE STUDY: The aim of this prospective multicentric study was to compare two different types of pain drawings in terms of acceptance and gain of information in patients with orofacial pain. PATIENTS AND METHODS: A total of 204 patients from 9 centers, who visited their dentist or physician for orofacial pain, received two different diagrams for pain drawings in random order. One was the original pain diagram of the Deutsche Schmerzfragebogen (German Pain Questionnaire, diagram A), and the other diagram had been developed to achieve a symmetrical representation of the body and to allow computer-assisted analysis (diagram B). This diagram was larger and contained a drawing of the head. The patients' answers were analyzed for the preference between diagrams, the number and distribution of pain areas, and the concordance between the diagrams. The results were correlated with the patients' data. RESULTS: Data from 183 patients could be analyzed: 100 of 183 patients preferred diagram B and 57 of 183 preferred diagram A, independent of gender, age, or duration of disease. Most patients reported pain in more than one area; in only 43 of 183 patients was the pain limited to the face and head. The number and distribution of pain areas were not different between the two pain diagrams. CONCLUSIONS: Detailed head and body diagrams can be used in the diagnostic evaluation of patients with orofacial pain without fear of placing excessive demands on the patients and are useful for detecting comorbidities.

[Recommendations for the standardized evaluation and classification of painful temporomandibular disorders: an update]. / Aktualisierung der Empfehlungen zur standardisierten Diagnostik und Klassifikation von Kaumuskel- und Kiefergelenkschmerzen.

BACKGROUND: In 2000, the interdisciplinary Working Group of Orofacial Pain within the German Chapter of the IASP (German Association for the Study of Pain) published recommendations for the standardized evaluation and diagnostic classification of patients with painful masticatory muscles and/or temporomandibular joints. The purpose of the present study was to critically review and update these recommendations. RESULTS: Appraisal of the relevant literature published after the release of the recommendations (up to December 2005) shows that the two-axis approach for the assessment of the somatic and psychosocial parameters of the orofacial pain experience has found wide support. Single aspects of the recommendations have been substantiated by additional scientific evidence. CONCLUSIONS: The recommendations reflect the current state of pain medicine. Therefore, they should be considered among practitioners who diagnose and manage patients suffering from temporomandibular disorders.

[Acute temporomandibular joint arthritis after Lyme borreliosis]. / Akute Kiefergelenkarthritis nach Lyme-Borreliose.

CASE REPORT: This report is about a rare connection between Lyme disease and an inflammation of the left temporomandibular joint. In this case, an infection was documented in 1998, 5 years after contact with Borrelia burgdorferi. The patient, a 49-year-old female, first came to our department in 1999. She showed the symptoms of a left temporomandibular joint infection. THERAPY: We suggested treatment with ceftriaxone 1 x 2 g/day i.v.

Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity.

The retinoblastoma tumor suppressor protein has been shown to bind directly and inhibit a transcriptionally-important amino-terminal kinase domain of TATA-binding protein-associated factor TAFII250. Cyclin D1 also is able to associate with the amino terminus of TAFII250 in a region very similar to or overlapping the Rb-binding site. In this study, we have examined whether cyclin D1 affects the functional interaction between Rb and TAFII250. We observed that when cyclin D1 is coincubated with Rb and TAFII250, the ability of Rb to inhibit TAFII250 kinase activity is effectively blocked. However, cyclin D1 by itself has no apparent effect on TAFII250 kinase activity. We further found that the Rb-related protein p107 can inhibit TAFII250 kinase activity, and this inhibition is likewise alleviated by cyclin D1. Cyclin D1 prevents the kinase-inhibitory effect of an Rb mutant unable to bind to D-type cyclins, indicating that it is acting through its association with TAFII250 and not with Rb. However, we found no evidence of TAFII250-binding competition between Rb and cyclin D1 in vitro. The adenovirus E1A protein, which also binds to both Rb and TAFII250, exhibited a suppressive effect on Rb-mediated kinase inhibition similar to that seen with cyclin D1. Our results suggest a novel means by which cyclin D1 may be able to independently regulate the activity of Rb.

Rb inhibits the intrinsic kinase activity of TATA-binding protein-associated factor TAFII250.

The retinoblastoma tumor suppressor protein, Rb, interacts directly with the largest TATA-binding protein-associated factor, TAFII250, through multiple regions in each protein. To define the potential role(s) of this interaction, we examined whether Rb could regulate the intrinsic, bipartite kinase activity of TAFII250. Here, we report that Rb is able to inhibit the kinase activity of immunopurified and gel-purified recombinant TAFII250. Rb inhibits the autophosphorylation of TAFII250 as well as its phosphorylation of the RAP74 subunit of TFIIF in a dose-responsive manner. Inhibition of TAFII250 kinase activity involves the Rb pocket (amino acids 379 to 928) but not its amino terminus. In addition, Rb appears to specifically inhibit the amino-terminal kinase domain of TAFII250 through a direct protein-protein interaction. We further demonstrate that two different tumor-derived Rb pocket mutants, C706F and Deltaex22, are functionally defective for kinase inhibition, even though they are able to bind the amino terminus of TAFII250. Our results suggest a novel mechanism of transcriptional regulation by Rb, involving direct interaction with TAFII250 and inhibition of its ability to phosphorylate itself, RAP74, and possibly other targets.

H-dependent formation of 5-aminolaevulinic acid-induced protoporphyrin IX in fibrosarcoma cells.

pH-Dependent variations in the fluorescence intensity of 5-aminolaevulinic acid-induced 5-aminolaevulinic acid protoporphyrin IX (PP IX) were compared with the cell viability following light irradiation. The fluorescence intensity was determined by flow cytometry and the cell activity was investigated by a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 24 h after photodynamic treatment. The results obtained by fluorescence measurements clearly showed that pH values of the incubation medium containing (5-ALA) below and above pH 7.4 led to a significant decrease in the fluorescence intensity. The viability of cells incubated with 0.6 mM 5-ALA in a medium at pH 6.0 was unaffected on exposure to light at lambda = 635 nm up to 15 J cm-2. However, cells incubated at pH 7.4 (with the other treatment parameters the same) were nearly completely destroyed. In addition, depletion of intracellular PPIX was faster in physiological medium than in acid medium.

Rb interacts with TAF(II)250/TFIID through multiple domains.

The retinoblastoma tumor suppressor gene product (Rb) binds directly to the largest TFIID subunit, TATA-binding protein associated factor TAF(II)250, first identified as the cell cycle regulatory protein CCG1. Here we map the domains in Rb and TAF(II)250 important for their interaction in vitro and in vivo. Both the amino terminus and the large pocket of Rb are able to associate independently with TAF(II)250. The binding domain(s) within the large pocket are distinct from the viral oncoprotein and E2F binding region since certain pocket mutations, which abolish E1A binding, do not abolish TAF(II)250 binding. Consistent with the large pocket of Rb binding to TAF(II)250, the large pocket domains of both p107 and p130 are able to bind to TAF(II)250 in vivo. We also demonstrate that at least two regions of TAF(II)250 are able to bind to the large pocket of Rb independently whereas the amino terminus of Rb binds to a distinct domain in TAF(II)250. We further demonstrate that Rb can bind to TFIID in vitro, presumably in part through an interaction with TAF(II)250. Our results suggest a complex interaction between Rb and TAF(II)250 and imply that TAF(II)250, TFIID, and potentially other basal transcription factors are targets for regulation by Rb and Rb-related proteins.

Carpal instability non-dissociative.

A retrospective study of 45 patients with symptoms of wrist pain and weakness with clinical evidence of instability is presented. These patients had normal intrinsic interosseous ligaments demonstrated arthrographically or surgically. They were followed for a minimum of 18 months and an average of 5.8 years. All patients demonstrated instability of the proximal carpal row which is referred to as carpal instability non-dissociative (CIND). Seven patients were treated non-operatively and 38 were treated operatively. Surgical management consisted of soft tissue reconstruction directed at the area of instability in 34 cases, joint levelling osteotomy in six, three of whom also had soft tissue reconstructions, and mid-carpal fusion in one. The overall good and excellent results were a disappointing 56% and there was no significant difference between the non-surgical and surgical groups. The best results were found in the ulna-minus CIND patients who underwent a joint levelling osteotomy, with 83% good and excellent results. CIND is associated with extrinsic ligamentous laxity; however, significant difficulty exists in locating the precise areas of maximum pathology. This accounts for the unpredictable results of treatment. As our understanding of the pathomechanics of CIND improves, the treatment will become more specific and the results should improve.

[Radical conjunctivectomy in therapy of malignant melanoma of the conjunctiva]. / Radikale Konjunktivektomie bei der Therapie des malignen Melanoms der Bindehaut.

BACKGROUND: In tumor excision of large malignant melanomas of the conjunctiva or in the excision of widespread precancerous melanosis the development of symblepharon is a threatening complication after conjunctivectomy, especially if the conjunctival fornix is afflicted. PATIENTS: Three patients with suspected nodular melanoma and surrounding precancerous melanosis of the conjunctiva were treated by extended excision of the conjunctiva. Instead of a conjunctival graft, spontaneous epithelization under the protection of an 'Illig' contact lens was achieved. After this, two patients with histologically proven malignant melanomas were treated by beta-ray radiation with 90-Strontium. RESULTS: Within four weeks after the excision a complete epithelization of the wound occurred and the functional as well as the cosmetic results were very satisfying. During the follow-up between 12 and 22 months no recurrence of the melanomas and no formation of symblepharon was observed. CONCLUSIONS: With regard to these results extended tumor excision without conjunctival graft seems to be a reasonable therapy for large nodular melanomas and widespread melanosis, while the application of an 'Illig' contact lens avoids the formation of symblepharon.

[Extended diagnosis of color-coded Duplex sonography by ultrasound contrast media. Imaging of movements of the urinary tract and tubes in animal experiment]. / Erweiterung der Diagnostik der farbkodierten Duplexsonographie durch Ultraschallkontrastmittel. Darstellung von Bewegungen in den Harnwegen und Tuben im Tierexperiment.

In colour-coded Duplex sonography, ultrasound contrast agents produce a significant enhancement of Doppler signals from the blood. Animal experiments were performed to examine whether a combination of colour-coded Duplex sonography and ultrasound contrast agents can also visualise movements from hollow spaces which do not normally contain scatteres (or an insufficient number of them). The animal experiments showed that the method can visualise both movements in the tubae and a vesicoureteral reflux. This opens up new diagnostic possibilities for ultrasound, which, however, still require rechecking by means of clinical studies.

[Color-coded duplex sonography and ultrasound contrast media--detection of renal perfusion defects in experimental animals]. / Farbkodierte Duplexsonographie und Ultraschallkontrastmittel--Nachweis von renalen Perfusionsdefekten im Tierexperiment.

The diagnostic use of microbubble consisting transpulmonary ultrasound contrast media in combination with color-coded duplex sonography (CCDS) has not been evaluated. Perfusion of the orthotopic kidney was therefore examined in an animal experiment with CCDS and transpulmonary echocontrast agent. The contrast agent consists of tiny stabilized air bubbles which survive the lung passage after peripheral venous injection and cause echo-enhancement of the arterial blood. The combination of CCDS and this contrast agent permits demonstration of the renal perfusion including the peripheral parenchyma. Even small experimental perfusion defects can be identified by this method. The use of this contrast agent in combination with CCDS might contribute significantly to the diagnostic potential of ultrasound.

Management of simple camptodactyly.

From a review of 57 patients with flexion deformity of the fingers (camptodactyly), 21 patients with 38 digits treated operatively had 18% good or excellent results, whereas 14 patients (41 digits) treated conservatively had 66% good or excellent results. Mild deformities responded well to splints and stretching. Moderate deformities treated operatively gained extension but at the loss of finger flexion. Severe deformities had improvement in extension (averaging 19 degrees in operative cases and 27 degrees in conservative), but there was significant loss of flexion in the operative group. Overall, 16 of 21 patients had loss of flexion after operative treatment. Conservative treatment of camptodactyly is recommended for digits with less than 60 degrees lack of extension. Operative treatment should be reserved for failed conservative treatment. Early joint motion post-operatively appears essential and surgical procedures that immobilize the P.I.P. joints should be avoided.

Blood flow evaluation of vascularized bone transfers in a canine model.

Blood flow in vascularized bone transfers was evaluated in a canine model. Cortical bone blood flow was determined in undisturbed control bone, vascularized heterotopic bone transfers, and nonvascularized cortical bone grafts by means of the radionuclide-labeled microsphere technique. Four animals were studied at 2 days, three at 1 week, eight at 2 weeks, four at 4 weeks, and three at 6 weeks postoperatively. In the 2-day animals, the vascularized bone transfers exhibited intermediate levels of blood flow (1.4 +/- 0.4 ml/100 g of bone/min) compared with undisturbed control bone (2.7 +/- 0.5 ml/100 g of bone/min) and conventional cortical bone grafts (0.0 +/- 0.0 ml/100 g of bone/min). At 1 week postoperatively, the differences in blood flow values of the vascularized transfers (1.7 +/- 0.7 ml/100 g of bone/min) and control bone (1.4 +/- 1.0 ml/100 g of bone/min) and of the nonvascularized grafts (0.2 +/- 0.1 ml/100 g of bone/min) and control bone (1.6 +/- 1.1 ml/100 g of bone/min) were no longer significant. At 2 weeks postoperatively, blood flow had increased in both graft groups. At 4 weeks postoperatively, the bone blood flow values in the vascularized transfers (4.8 +/- 1.4 ml/100 g of bone/min) were significantly greater than the bone blood flow in control specimens (1.6 +/- 0.5 ml/100 g of bone/min) and conventional cortical bone grafts (2.5 +/- 2.0 ml/100 g of bone/min).(ABSTRACT TRUNCATED AT 250 WORDS)