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Biomedical subjects

M B Nielsen

Publications and source records attributed to M B Nielsen.

At least 19 recordsLinked to original sources
PubMed2006

Ultrasound Doppler of the Achilles tendon before and after injection of an ultrasound contrast agent--findings in asymptomatic subjects.

UNLABELLED: The sensitivity of ultrasound Doppler has now reached a level at which perfusion can be detected even in normal, resting musculoskeletal tissues. To be able to distinguish normal from abnormal flow, the resistive index (RI) determined by spectral Doppler may be of value. Inflammation is associated with low RI values and a value of 1.00 is normal. PURPOSE: In tissues with no detectable flow, it has been assumed that RI may be defined as 1.00. This study was performed to test if normal tendinous vessels could be visualised with a contrast agent, and if such vessels had normal RI. MATERIALS AND METHODS: Ultrasound (US) was performed with a 14 MHz linear transducer. 22 asymptomatic tendons in 12 subjects were scanned, and only 5 ultrasonically normal tendons in 5 subjects were identified. In these 5 normal tendons, SonoVue was used to make vessels visible. The Achilles tendons and the peritendinous tissues were evaluated clinically. RESULTS: In all 5 ultrasonically normal tendons, arteries could be detected with Doppler after contrast injection and in all cases with normal RI values. All vessels were located in the mid-portion of the tendon. 18 tendons were categorised as normal by the clinician. CONCLUSION: After administration of a contrast agent, all Achilles tendons could be demonstrated to have arteries present in the mid-portion. The flow profile of these arteries was fully normal without diastolic component and with an RI of 1.00. This finding has implications for criteria of normality of tendons, which cannot be based exclusively on the presence or absence of Doppler activity. The majority of the tendons in this study had ultrasound abnormalities both on gray-scale and colour Doppler. It can be speculated that the abnormalities may be age-related degenerative changes and that age-stratified normal materials are needed to define normality. There was no consistency between US and clinical diagnosis.

Achilles Tendon↗
PubMed2006

Detection rate of periintestinal lymph nodes.

AIM: Compared to standard two-dimensional (2D) endosonography, three-dimensional (3D) endosonography has been presented as a possible improvement regarding imaging of the gastrointestinal (G-I) tract and detection of metastatic lymph nodes. The aim of this study was to evaluate the efficacy of detecting periintestinal lymph nodes in surgical specimens using 3D endosonography. PATIENTS AND METHODS: Surgical specimens from 31 patients with malignant G-I tumours were investigated by 3-D endosonography and histology with focus on the presence of periintestinal lymph nodes and presence of metastasis. The specimens were scanned submerged into water. Position and size of the lymph nodes were mapped on a photo of the specimen both by the pathologist and the examiners. RESULTS: Three-dimensional endosonography detected 48 out of 60 malignant lymph nodes (80.0 %), and 110 out of 219 benign lymph nodes (50.2 %). The positive predictive value for an endosonographic finding interpreted as a lymph node was 0.97. CONCLUSION: The detection rates for periintestinal lymph nodes were relatively high and seemed superior to the one usually assigned to 2D endosonography. Although distinguishing between metastatic and non-metastatic lymph nodes remains a problem, all patients with histologically confirmed metastasis to lymph nodes were detected by 3D endosonography, and the technique thus seems suitable for grouping of patients prior to surgery.

Colonic Neoplasms↗
PubMed2005

Doppler ultrasound findings in healthy wrists and finger joints before and after use of two different contrast agents.

OBJECTIVE: To examine the effect of contrast agents on Doppler ultrasound findings in the synovial membrane in the wrist and fingers of healthy volunteers. MATERIALS AND METHODS: Eleven healthy subjects were included in the study (5 women and 6 men, mean age 38 years, range (20-60)). They had no clinical signs of inflammatory or degenerative joint diseases. A total of 66 joints were examined-6 joints for each subject: wrist and metacarpophalangeal (MCP) joints 1-5-before contrast injection and after Levovist and SonoVue injection with a 30 minute interval. RESULTS: Colour Doppler activity was detected in 10/55 (18%) MCP joints before contrast injection and in 29/55 (53%) and 28/55 (51%) joints after Levovist (p<0.0001) and SonoVue injection (p = 0.0001), respectively. A significant increase in Doppler activity in the radial (p<0.05) and ulnar (p = 0.01) parts of the wrist joint was detected only after SonoVue injections. With spectral Doppler no difference was found in the resistive index (RI) in the vessels measured before as compared with those only detected after contrast injection. CONCLUSION: The number of joints with colour Doppler activity in healthy volunteers was increased by the use of contrast agents. No changes in RI were detected. The value of contrast agents remains to be demonstrated in inflammatory diagnostics.

Adult↗
PubMed2005

Ultrasound-guided drainage of breast abscesses: results in 151 patients.

The aim of this paper is to describe the efficacy of ultrasound-guided drainage of breast abscesses with special attention to the risk of recurrence and the need for surgical treatment in a consecutive patient population. 151 patients, 89 with puerperal and 62 with non-puerperal breast abscesses, were treated with ultrasound-guided drainage, by needle or catheter under local anaesthesia. Follow-up punctures were performed at 2 or 3 day intervals until the clinical condition and ultrasound findings had improved. All patients were treated with oral antibiotics. Mammography was performed to search for underlying cancer. 86 (97%) out of 89 patients with puerperal abscesses and 50 (81%) out of 62 with non-puerperal abscesses recovered after the first round of ultrasound-guided drainage. One patient in each group had recurrence in loco but recovered after further ultrasound-guided drainage. 13 patients, 11 with non-puerperal and two with puerperal abscesses, underwent surgical excision of the abscess cavity or fistulas. Breastfeeding continued and 117 patients were treated as outpatients. The median number of follow up examinations in the ultrasound-department was four (range 1-10) for the group of patients with puerperal abscess and three (range 1-7) in the group of patients with non-puerperal abscess. The corresponding figure for the median number of punctures was for both groups one (range 1-6 and 1-4). There were no reports of newly diagnosed breast cancer in the 2 year follow-up period. This study supports the use of ultrasound-guided drainage in puerperal and non-puerperal breast abscesses. The method is less invasive than traditional surgery and has a high rate of success.

Abscess↗
PubMed2005

Three-dimensional anal endosonography may improve diagnostic confidence of detecting damage to the anal sphincter complex.

The aim of study was to investigate the differences between three-dimensional (3D) endosonography and two-dimensional (2D) endosonography in visualizing damage to the anal sphincter complex. 33 patients with a history of damage to the anal sphincters were examined with a 10 MHz rotating endoprobe. Cross-sectional images of the anal sphincters were stored on a 3D system during retraction of the endoprobe through the anal canal. Cross-sectional images (2D) were compared with reconstructed projections (3D) according to five parameters relating to damage of different parts of the sphincter muscles as well as scar-tissue formation in the rectovaginal septum. Depending on whether the investigator felt confident in diagnosis of scar tissue being present or not a numerical value of 1 or 0 was assigned. In this way a scale from 0 to 5 points was achieved, which ideally should be identical in 3D and 2D. Overall both observers felt diagnostic confidence in a median of five parameters (range 4-5) using 3D, compared with a median of four parameters (range 3-5) using 2D (p=0.001). When only assessing the four parameters relating to damage of different parts of the sphincter-muscles the observers felt diagnostic confidence in eight more cases using 3D than 2D. This difference did not reach statistical significance. The overall agreement between the two observers comparing all five parameters was 98.2% using 3D and 87.9% using 2D. 3D anal endosonography improves diagnostic confidence in detecting damage to the anal sphincter complex. The agreement between the two observers was acceptable using 2D but better when using 3D. The 3D method may improve the selection of patients for surgical repair of the anal sphincter complex.

Adult↗
PubMed2001

Highly functionalized dimeric tetraethynylethenes and expanded radialenes: strong evidence for macrocyclic cross-conjugation.

A selection of dimeric tetraethynylethenes (TEEs) and perethynylated expanded radialenes, containing different donor/acceptor substitution patterns, have been prepared and fully characterized. The first X-ray crystal structure of an expanded [6]radialene, with twelve peripheral 3,5-di(tert-butyl)phenyl substituents, is presented. This macrocycle, the all-carbon core of which is isomeric with fullerene C60, adopts a non-planar, "chair-like" conformation. Also a TEE dimer, carrying N,N-dimethylaniline donor substituents, has been subjected to an X-ray crystallographic analysis. The electronic properties were studied by UV/Vis spectroscopy and electrochemistry, providing fundamental insight into mechanisms of pi-electron delocalization in the acyclic and macrocyclic chromophores. Donor or donor-acceptor-substituted dimeric TEE derivatives show very strong absorptions extending over the entire UV/Vis region; their longest wavelength absorption bands have high charge-transfer character. Macrocyclic cross-conjugation in the expanded radialenes becomes increasingly efficient with increasing donor-acceptor polarization. A dual, strongly solvent-polarity-dependent fluorescence was observed for a tetrakis(N,N-dimethylaniline)-substituted dimeric TEE; this interesting emission behavior is explained by the twisted intramolecular charge-transfer (TICT) state model. Donor-substituted expanded radialenes display huge resonance-enhanced third-order nonlinear optical coefficients.

Journal Article↗
PubMed2001

Binding studies between tetrathiafulvalene derivatives and cyclobis(paraquat-p-phenylene).

The complexation between a number of different pi-electron donating TTF derivatives and the pi-electron accepting tetracationic cyclophane cyclobis(paraquat-p-phenylene) (CBPQT(4+)) has been studied by (1)H NMR and UV-vis spectroscopy. The results demonstrate that the strength of association between the donors (TTF derivatives) and acceptor (CBPQT(4+)) is strongly dependent on the pi-electron donating properties (measured by the first redox potential ) of the TTF derivatives. However, the first redox potential () is not the only factor of importance. The extended pi-surface of the TTF derivatives also exerts a stabilizing influence upon complexation. The kinetics for the complexation-decomplexation were studied using (1)H NMR spectroscopy and are related to the bulkiness of the TTF derivatives. These effects may serve to improve the design of interlocked molecular systems, especially (bistable) molecular switches, in which CBPQT(4+) and a derivatized TTF unit are incorporated.

Journal Article↗
PubMed2001

Kinetics of TCR use in response to repeated epitope-specific immunization.

Selection of T cell-directed immunization strategies is based extensively on discordant information derived from preclinical models. We characterized the kinetics of T cell selection in response to repeated antigenic challenge. By enumerating with epitope/HLA tetrameric complexes (tHLA) vaccine-elicited T cell precursor frequencies (Tc-pf) in melanoma patients exposed to the modified gp100 epitope gp100:209-217 (g209-2M) we observed in most patients that the Tc-pf increased with number of immunizations. One patient's kinetics were further characterized. Dissociation kinetics of g209-2M/tHLA suggested enrichment of T cell effector populations expressing TCR with progressively higher affinity. Furthermore, vaccine-elicited T cells maintained the ability to express IFN-gamma ex vivo and proliferate in vitro. Thus, repeated exposure to immunogenic peptides benefited immune competence. These results provide a rationale for immunization strategies.

Cancer Vaccines↗
PubMed2001

Unmasking cryptic epitopes after loss of immunodominant tumor antigen expression through epitope spreading.

The basis of intra-tumoral and systemic T cell reactivity toward cancer remains unclear. In particular the role that peripheral stimuli, whether endogenous or exogenous, play in shaping acquired immune response toward cancer remains poorly understood. In this study we document the surfacing of systemic immune reactivity toward a cryptic epitope from the MAGE-12 gene (MAGE-12:170-178), after temporary regression of a single melanoma metastasis, in response to gp100/PMel17-specific vaccination. This emergence was unlikely related to unusually high expression of MAGE-12 by the tumor, by the influence of analog epitopes to MAGE-12:170-178. Because MAGE-12 was unlikely to be expressed at sites other than the tumor, the demonstration of MAGE-12:170-178 reactivity in post- but not pre-vaccination circulating lymphocytes suggests that the systemically observed immune response was influenced by events induced by the vaccine at tumor site or draining lymph nodal areas. Possibly, as suggested by pre-clinical models, immunologic ignorance is the default response toward cancer in humans unless unusual stimulatory conditions occur in peripheral tissues. Surfacing of MAGE-12 specificity occurred in association with loss of gp100/PMel 17 targeted by the vaccine. This finding suggests that vaccinations might have effects beyond their intrinsic specificity and may trigger broader immune responses through epitope spreading by inducing changes within the tumor microenvironment. This may have important practical implication for the development of immunization strategies. Published 2001 Wiley-Liss, Inc.

Alleles↗
PubMed2001

Hepatic vein transit time of an ultrasound contrast agent: simplified procedure using pulse inversion imaging.

The aim of this study was to ascertain whether a new ultrasound technique, namely pulse inversion imaging, could assess the arrival of a contrast agent in the hepatic veins, and to describe possible advantages of this procedure in determining transit time over a previously described method based upon spectral Doppler quantification. 15 subjects were scanned using pulse inversion imaging. A bolus injection of 2.5 g Levovist (Schering AG, Berlin, Germany) 300 mg x ml(-1) was given into an antecubital vein. Median transit times of 16 s (range 14-20 s) were found in patients with liver cirrhosis (n=4), 22 s (range 16-27 s) in patients with focal liver lesions (n=8) and 31 s (range 30-32 s) in control subjects (n=3). The maximum interobserver variation was 2 s and the maximum intraobserver variation was 3 s (n=10). Transit time was assessed by both pulse inversion imaging and spectral Doppler quantification in six patients. Comparison of the two methods showed transit times within 2 s apart in five patients and within 5 s apart in one patient. In conclusion, it is possible to assess transit time using pulse inversion imaging. This method is simpler than a previously described method requiring computer analysis. Moreover, several liver veins can be assessed simultaneously. Different transit times were observed in different liver veins in two patients with liver tumours. A short transit time (<27 s) appears to be found only in patients with liver disease. After transit time assessment, it is possible to use the injected contrast agent for late phase imaging of the liver parenchyma.

Adult↗
PubMed2000

Status of activation of circulating vaccine-elicited CD8+ T cells.

Selective blunting of the status of activation of circulating tumor-specific T cells was invoked to explain their paradoxical coexistence with unhampered tumor growth. By analogy, lack of tumor regression in the face of observable melanoma vaccine-induced T cell responses might be attributed to their status of activation. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited T cell precursor frequency directly in PBMC of patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope (g209-2 M). Furthermore, we tested by intracellular (IC)-FACS analysis and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to produce cytokine in response to challenge with vaccine-related epitopes or vaccine-matched (HLA-A*0201) melanoma cells. Vaccine-induced enhancement of T cell precursor frequency could be detected with tHLA in PBMC from six of eight patients studied at frequencies ranging between 0.3 and 2.3% of the total CD8+ population. Stimulation with vaccine-related epitopes induced IFN-gamma expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of these patients. Furthermore, down-regulation of tHLA staining was noted upon cognate stimulation that could be utilized as an additional marker of T cell responsiveness. Finally, we observed in six patients an enhancement of reactivity against vaccine-matched tumor targets that was partly independent of documented vaccine-specific immune responses. A strong correlation was noted between tHLA staining of postvaccination PBMC and IFN-gamma expression by the same samples upon vaccine-relevant stimulation and assessed either by IC-FACS or qRT-PCR. Thus, blunting of the status of T cell activation on itself cannot easily explain the lack of clinical responses observed with vaccination.

Antigen Presentation↗
PubMed2000

Melanoma vaccines: the paradox of T cell activation without clinical response.

In recent years significant progress in the understanding of the immune biology of melanoma has evolved from the identification of melanoma antigens (MAs) recognized by T cells. MAs consist of intracellular proteins that are expressed on the surface of cancer cells in association with human leukocyte antigen (HLA) class I molecules and therefore are suitable targets for cytotoxic T lymphocytes (CTLs). Several new monitoring strategies have been implemented to evaluate the status of activation and localization of vaccine-induced T cells in the peripheral circulation as well as the tumor site, including limiting dilution, in vitro sensitization, and ELISPOT. Previous studies aimed at monitoring patients receiving vaccination have utilized mainly those three methods. These methods have demonstrated that antigen-specific vaccination can elicit immune responses detectable in the peripheral blood of immunized patients. These assays, however, have been faulted by their requirement for in vitro expansion of T cells (limiting dilution or in vitro sensitization) or for limited sensitivity (ELISPOT). More recently, the use of soluble HLA/peptide complex tetramers, intracellular fluorescence-activated cell sorting (FACS) analysis, and real-time polymerase chain reaction (PCR) has been proposed for the monitoring of vaccine trials. These methods have the appeal of allowing direct enumeration of T cells specific for a particular epitope within relevant samples such as peripheral blood lymphocytes, lymph nodes, and tumors. We are evaluating whether utilizing a combination of HLA/peptide tetramer (tHLA) together with Taqman-based real-time reverse-transcription (RT)-PCR and intracellular FACS analysis could establish a direct and comprehensive strategy for the assessment of epitope-specific immune response in vivo. In conditions close to those of the tumor microenviroment or in peripheral blood lymphocytes, however, a different status of T cell activation can be expected due to a direct stimulation of T cells by tumor or antigen-presenting cells. We observed that activated T cells can easily be detected in the peripheral blood of patients who have received MA-specific vaccines. However, when T cells are stimulated with their relevant epitope, a high level of T cell receptor downregulation occurs that does not allow identification of vaccine-specific T cells directly with tHLA. Thus evaluation of epitope-specific T cells at the tumor site, where they might be exposed to stimulation by interaction with tumor cells and/or in bulk peripheral blood mononuclear cells, might be more efficiently analyzed with functional methods such as intracellular FACS and Taqman-based real time RT-PCR.

Antigens, Neoplasm↗
PubMed2000

The effects of atropine on dynamic compliance in healthy intubated adults.

In order to compare the effect of atropine and sodium chloride on the dynamic compliance of the respiratory system after tracheal intubation, we studied 20 patients allocated randomly into two groups to receive either: atropine after 5 min of steady state and sodium chloride after 10 min (group A) or in reverse order (group B) intravenously. The study was conducted in a randomized double-blinded manner. The patients were anaesthetized with thiopental 5 mg kg(-1) followed by thiopental 50 mg intravenously, as required. Intubation was facilitated by atracurium 0.5 mg kg(-1) intravenously and fentanyl 200 microg intravenously. During fixed volume ventilation (100 mL kg(-1), f=10), compliance and end-tidal carbon dioxide were measured every 10 s by a Datex AS/3-respiratory module connected to a portable IBM-pc. Five minutes was allowed to establish a steady state then either atropine or sodium chloride was administered according to the protocol. Respiratory dynamic compliance increased significantly after intravenous administration of atropine (P < 0.05). We conclude that atropine 1.0 mg given intravenously provides protection against an intubation-induced decline in respiratory dynamic compliance.

Adolescent↗