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Biomedical subjects

R Felix

Publications and source records attributed to R Felix.

At least 37 records · Page 2Linked to original sources

In a resource-poor country, mutation identification has the potential to reduce the cost of family management for hereditary nonpolyposis colorectal cancer.

PURPOSE: Colonoscopic surveillance of family members at risk of hereditary nonpolyposis colorectal cancer is difficult in a resource-poor country because of its expense. For family members who live in remote areas, poor communication and limited access to sophisticated medical care make surveillance even more difficult. The identification of the mutation causing the disease will simplify surveillance. Our aim was to assess the impact of mutation analysis on the management of a South African family with more than 150 members at risk for hereditary nonpolyposis colorectal cancer. METHODS: We studied a family that met the Amsterdam criteria for hereditary nonpolyposis colorectal cancer. Colorectal cancer affected 27 members in three generations (evidence from histology in 12, barium enema in 1, and family statements in 14 family members). Leukocyte DNA from family members was tested for linkage to candidate loci for colorectal cancer, and DNA from formalin-fixed cancers from six family members was studied for microsatellite instability. DNA from all available family members was then screened for mutations in the hMLH1 gene. The number of individuals at 50 percent risk was calculated by family pedigree and compared with the number who have the mutation. RESULTS: A disease-causing mutation in exon 13 of hMLH1 segregated with the disorder in members of this kindred. Test results of 100 chromosomes from population-matched controls were negative. Sixty family members between the ages of 16 and 50 years are at 50 percent risk for colon cancer by pedigree analysis, but of these, only 26 (43 percent) have the mutation. CONCLUSION: A mutation in the DNA repair gene hMLH1 was found in family members with hereditary nonpolyposis colorectal cancer and in some unaffected relatives previously at 50 percent risk, but not in unrelated subjects. The blood test for the mutation will simplify management, counseling, and surveillance and help to establish prophylactic colectomy.

Chromosome Segregation

[Phase II study on preoperative radio-chemo-thermotherapy in locally advanced rectal carcinoma].

BACKGROUND: Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas. PATIENTS AND METHODS: Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m2) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed. RESULTS: Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T90, cum min T90 > or = 40.5 degrees C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too. CONCLUSIONS: Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.

Adult

[Dose distribution in conventional CT and spiral CT and on the topic of dose reduction with spiral CT].

OBJECTIVE: To compare spiral CT with conventional CT with regard to the dose distribution in the irradiated body and to examine when an increase in the table feed in spiral CT leads to a dose reduction compared with conventional CT. METHODS: In order to show the dose distribution, films were exposed in an acrylic phantom. The nominal slice thickness was 5 mm; the slice distance in conventional CT was 5 and 10 mm; the table feed in spiral CT was 5 and 10 mm per rotation (pitch 1 and 2). The integral doses delivered in spiral CT and conventional CT were related to the table feed per rotation or slice distance, respectively, and were compared arithmetically with each other. RESULTS: Spiral CT showed reduced dose fluctuations in axial direction compared with conventional CT. Only in conventional CT with a slice distance of 5 mm did the axial dose distribution show relative dose peaks near the rotation axis. The longer the body region to be examined is, the less table feed is necessary in spiral CT for a dose reduction. From a length of 15 times the slice thickness, a pitch of > 1.1 leads to a reduction of the integral dose compared with conventional CT. CONCLUSIONS: The continuous table feed in spiral CT results in evenly distributed axial dose distributions compared with the discontinuous scanning in conventional CT. The spiral technique can give an important contribution to dose reduction in CT.

Equipment Design

[2D and 3D parameter images for the analysis of contrast medium distribution in dynamic CT and MRI].

AIM: For dynamic contrast medium (CM) studies, parameter images exploit specific features of the time/intensity curve (TIC) of each pixel and represent these values in a new image. Existing concepts of two-dimensional CM analysis are extended for three-dimensional applications using adequate computer graphic visualization. METHODS: Imaging: intravenous CM injection; first-pass analysis using fast CT acquisition of a single slice; CM accumulation by 40 MR slices (6 sequences every 90 s = 240 images): Software: TIC of arbitrary 2D/3D regions; parameter images: (1) temporal maximum intensity projection (TMIP) of all voxels over time, (2) temporal CM gradients (TG) based on TIC amplitude, (3) TIC slope, (4) time of TIC peak, (5) correlation coefficient to reference TIC. The calculated 3D data of CM accumulation was visualized using multiplanar reformation, MIP, surface reconstruction, volume rendering, texture mapping and animation. RESULTS: In first-pass analyses, TMIP and TG allowed the simultaneous or separated presentation of different temporal phases of the CM bolus. Correlation images emphasized regions with similarities to given TIC patterns. Three-dimensional computer graphic techniques enabled (1) anatomical/functional mapping of original image and CM accumulation and (2) fused display of both spatial CM enhancement and color-encoded time of TIC peak in one common image. CONCLUSIONS: The quantification of presence, magnitude, and time-of-peak of CM accumulation in local image regions supports the assessment of vascularization and of ischemic or necrotic areas.

Breast Neoplasms

[Morphologic image processing operators: reduction of partial volume effects for improved 3D visualization of CT data].

AIM: The quality of segmentation and three-dimensional reconstruction of anatomical structures in tomographic slices is often impaired by disturbances due to partial volume effects (PVE). The potential for artefact reduction by use of the morphological image processing operators (MO) erosion and dilation is investigated. DESIGN: The CT examinations of 31 patients with pathological alterations in lung or brain were segmented using automatic region growing and the MO were applied in a different number of iterations. The processed regions were 3D-reconstructed (shaded surface display, MIP, volume rendering) and the occurrence of PVE-related artefacts using the signal-to-background ratio (SBR) prior to and after MO application was compared. RESULTS: For all patients under review, the artefacts caused by PVE were significantly reduced by erosion (lung: mean SBRpre = 1.67, SBRpost = 4.83; brain: SBRpre = 1.06, SBRpost = 1.29) even with only a small number of iterations. Region dilation was applied to integrate further structures (e.g. at tumor borders) into a configurable neighbourhood for segmentation and quantitative analysis. CONCLUSIONS: The MO represent an efficient approach for the reduction of PVE artefacts in 3D-CT reconstructions and allow optimized visualization of individual objects.

Densitometry

[Electron-beam computed tomography in heart surgery].

PURPOSE: Electron beam CT (EBCT) has been devised to improve the imaging of the heart and the great vessels. Therefore, this method is expected to facilitate the imaging workup of patients referred for cardiothoracic surgery. We set out to review the most important surgical issues that can be addressed with this method. METHODS: From June, 1997 until July, 1998, more than 300 patients were referred from cardiothoracic surgery. In a retrospective analysis, diagnostic results were reviewed and compared with surgical findings and the clinical course. RESULTS: Aortocoronary bypass graft occlusions were detected with a sensitivity of 100% and a specificity of 95%. Calcifications of the aorta, pericardium and intracardiac tumors were surgically confirmed in all instances. There was a significant association of the degree of coronary artery calcification and the progression of cardiac allograft vasculopathy in 50 heart transplant recipients. In EBCT of the aorta, a high degree of diagnostic confidence was found for aortic dissection, aortic wall hematoma or aortic perforation. CONCLUSIONS: We conclude that EBCT represents an important diagnostic tool both for surgical planning and postoperative surveillance in cardiothoracic surgery.

Adult

[Diagnosis of the abdominal vascular system by means of electron-beam computed tomography (EBT)].

PURPOSE: To evaluate the potential of electron-beam computed tomography (EBT) in the pre- and postinterventional assessment of vascular abdominal pathologies. MATERIAL AND METHODS: Forty patients with implanted transjugular portosystemic shunt (TIPS), 12 patients with peripheral arterial occlusive disease and 8 patients with infrarenal abdominal aortic aneurysm after endovascular implantation of bifurcation stents were prospectively examined with contrast-enhanced EBT during one year. The evaluation included analysis of time-density curves (TDC) and 3D reconstructions. Results were compared with Doppler sonography and/or DSA. RESULTS: In 30 of 40 TIPS patients, identical results were found with EBT, Doppler sonography and/or DSA. Reduced perfusions of the TIPS, which were subsequently confirmed by DSA, could not be shown with EBT in 3 patients. Nine of 12 patients with peripheral arterial occlusive disease and angiographically proven stenosis (> 75%) showed a reduced and delayed peak density of the time-density curves. The quantification of arterial stenosis, however, did not follow the angiographic values. In all patients with the implanted bifurcation stents, EBT could correctly exclude a leakage of the stent. CONCLUSION: EBT has certain advantages over conventional spiral CT in the evaluation of abdominal vascular pathologies due to the additional assessment of perfusion parameters. Clinical indications for the use of EBT are seen especially in the postinterventional follow-up of patients with implanted stents.

Abdomen

Morphological changes in chest radiographs of patients with acute respiratory distress syndrome (ARDS).

OBJECTIVE: To determine whether the quality of infiltrations in chest radiographs can accurately predict the histological extent of fibrotic change in patients with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective clinical investigation. SETTING: Intensive care unit (ICU) of a university teaching hospital. PATIENTS AND METHODS: Of 47 patients treated with extracorporeal membrane oxygenation (ECMO) for severe ARDS over a 5-year period, 23 patients underwent open lung biopsy at thoracotomy for treatment, mostly of pneumothorax. Chest films obtained by portable chest roentgenography preceding the operation were reviewed retrospectively and compared to the histomorphological results of the lung specimen. RESULTS: Chest radiographs displayed mixed alveolar-reticular opacification in 60.2%, alveolar patterns in 22.9% and reticular opacities in 10.5%. In 0.4% there were no infiltrates, 6% could not be evaluated because of insufficient quality. There was no relevant difference between the right and left lungs. Subdividing patients into two groups according to the histological results of either absent or mild (1) or severe (2) lung fibrosis, we found an alveolar haziness in 12.3% in group 1 compared with 28.2% in group 2, while reticular characteristics were identified in 13% and 11%, respectively. CONCLUSIONS: The most common opacity in chest radiographs of patients with severe ARDS treated with ECMO is mixed alveolar-reticular opacification. Severe lung fibrosis is not positively correlated with a reticular radiographic pattern. ECMO does not lead to specific radiological changes in conventional radiograms, contrary to clinical findings that treatment with ECMO might induce pleural or pulmonic haemorrhage, especially in the earlier days when systemic heparinization had to be used instead of the heparin-coated tube-surfacing.

Adolescent

Phorbol myristate acetate downregulates the binding sites for colony-stimulating factor-1 on osteoclasts isolated from rats.

Colony-stimulating factor-1 (CSF-1) is the growth factor for the cells of the mononuclear phagocytic system and for osteoclasts. We tested whether phorbol myristate acetate (PMA), a phorbol ester activating protein kinase C, modulates the number of binding sites for CSF-1 on isolated rat osteoclasts. PMA decreased binding of CSF-1 to osteoclasts within 60 minutes. The effect of PMA was dose dependent at concentrations between 10(-9) M and 10(-6) M. The inactive phorbol ester, 4alpha-phorbol 12,13-didecanoate, had only a slight effect. Since the osteoclast preparation was contaminated with other cells, the action of PMA on the osteoclasts might have been either direct or indirect. In pure osteoclasts harvested by a micropipette, the downregulation of CSF-1 binding by PMA reached only about three-quarters of that in nonpurified preparations. Addition of osteoblastic osteosarcoma UMR106 cells increased the effect of PMA. Antiserum against CSF-1, which was added to osteoclasts contaminated with other cells, mainly osteoblasts, partially inhibited the effect of PMA, but the antiserum had no effect in pure osteoclasts. These data suggest that the effect mediated by osteoblasts or other contaminating cells is due to the release of CSF-1, which is known to downregulate its binding sites on osteoclasts. The direct action of PMA on osteoclasts decreased the binding only to about 40%, in contrast to CSF-1 which completely downregulated the binding. The data also differ from the published results about macrophages. In these cells, PMA downregulates the binding of CSF-1 completely. The CSF-1 binding sites on osteoclasts recovered within 4 hours after removal of PMA, and cycloheximide, an inhibitor of protein synthesis, inhibited the recovery.

Animals

[High resolution functional magnetic resonance tomography with Gd-DTPA eyedrops in diagnosis of lacrimal apparatus diseases].

UNLABELLED: Both dacryocystography and dacryoscintigraphy are well established in the evaluation of stenoses of the lacrimal drainage system. They provide limited information about the ductal anatomy itself and about periductal structures. MR imaging was evaluated for its capability to directly visualize the lacrimal drainage system in detail and simultaneously provide functional characterization of dacryostenosis. SUBJECTS AND METHODS: Twenty-seven lacrimal drainage systems of 23 patients suffering from epiphora were examined in an MR unit before and after conjunctival and intravenous application of Gd-DTPA using a surface coil. RESULTS: Dacryostenosis was found in 23 of 27 lacrimal systems. Stenoses were localized to the canalicular (n = 3), saccular (n = 8), and ductal (n = 12) level, and were classified as stenosis or occlusion. CONCLUSION: MR imaging with conjunctival contrast application allows within one examination both detailed morphological and functional assessment of the lacrimal drainage system with depiction of surrounding structures. Limitations arise mainly from demands on technical and patient-related preconditions.

Contrast Media

The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit.

Stargazer mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear. We describe here a novel gene, Cacng2, whose expression is disrupted in two stargazer alleles. It encodes a 36-kD protein (stargazin) with structural similarity to the gamma subunit of skeletal muscle voltage-gated calcium (Ca2+) channels. Stargazin is brain-specific and, like other neuronal Ca2+-channel subunits, is enriched in synaptic plasma membranes. In vitro, stargazin increases steady-state inactivation of alpha1 class A Ca2+ channels. The anticipated effect in stargazer mutants, inappropriate Ca2+ entry, may contribute to their more pronounced seizure phenotype compared with other mouse absence models with Ca2+-channel defects. The discovery that the stargazer gene encodes a gamma subunit completes the identification of the major subunit types for neuronal Ca2+ channels, namely alpha1, alpha2delta, beta and gamma, providing a new opportunity to understand how these channels function in the mammalian brain and how they may be targeted in the treatment of neuroexcitability disorders.

Amino Acid Sequence

Delineation of maxillofacial cutaneous lesions by means of high-resolution magnetic resonance imaging.

To evaluate the use of high-resolution magnetic resonance imaging (MRI) for the differentiation of skin tumors in the maxillofacial region, 60 patients (25 female) were examined in a 1.5-T whole-body MR imager with a 2.5-cm surface coil. Plain transverse T1-(TR 500 ms, TE 25 ms), T2-(2200 ms, TE 80 ms), fat-(TR 500 ms, TE 28 ms), and water-suppressed (TR 500 ms, TE 38 ms) SE sequences were used. Following the application of the paramagnetic contrast agent Gd-DTPA, transverse T-weighted and fat suppression sequences were repeated. Before and after contrast administration, tumor signal intensities and percent contrast enhancement were determined by a ROI technique. All tumors were classified by standard histologic technique and evaluated with regard to their response to contrast medium. Quantitative evaluation was performed by three independent radiologists. Additionally, signal- and contrast-to-noise ratios were calculated for each tumor type. All MRI findings were compared with histology. Significant contrast enhancement occurred in most tumors; malignant tumors displayed inhomogeneous enhancement. The optimal pulse sequences for tumor delineation are plain T1-weighted, water-suppressed, and contrast-enhanced fat-suppressed sequences. Tumors could not be specified by signal intensities or percent contrast enhancement, and CNR did not allow for malignant lesions to be differentiated from benign tumors. High-resolution MRI proved to be an adequate method for imaging skin tumors and their inner structure. Tumor typing was not possible by either contrast-administration or modification of sequence parameters. In this regard, further innovations in contrast agent design seem to be necessary.

Adult

[Blood flow quantification in hemodialysis shunts by phase contrast magnetic resonance angiography (PC-MRA) compared with duplex sonography].

PURPOSE: Aim of this study was to evaluate whether phase contrast MR angiography (PC-MRA) could provide additional functional information besides morphology in the assessment of haemodialysis fistulae. MATERIAL AND METHOD: Twenty-two patients (11 male, 11 female), aged 22-77 years, were examined. MR images were obtained with a 1.5 T Gyroscan ACS-NT (Philips, Best, Netherlands) using a high-resolution wrap-around coil. In addition to MRA blood-flow measurements were performed with a gradient-echo sequence (TR 14 ms, TE 5-5.5 ms, flip-angle 15 degrees, 6 mm slice thickness, retrospective gating, matrix 96:128) in the venous and arterial section of the fistulae. Doppler flow measurements were performed at the same position with a Sonoline Elegra (Siemens AG, Erlangen) using a 7.5 MHz transducer. RESULTS: Both methods of flow-volume measurements showed a good correlation (r = 0.94 in the arterial section, r = 0.90 in the venous section, p < 0.001). The average calculated blood flow was measured 11% (arterial section) and 12.8% (venous section) higher with Pulsed Waved Doppler as compared to PC-MRA. CONCLUSION: PC-MRA with a high-resolution wrap-around coil is a reliable method for measuring functional parameters like flow-volume and flow velocity in haemodialysis fistulae and a useful complement to the visualisation capabilities of MRA.

Adult

[Verification of MR thermometry by means of an in vivo intralesional, fluoroptic temperature measurement for laser-induced thermotherapy ov liver metastases].

PURPOSE: To evaluate the correlation of MR-measured changes of signal intensity and invasive fluoroptic temperature measurements during MR-guided LITT of liver metastases. MATERIALS AND METHODS: In 15 patients with proven liver metastases of colorectal carcinoma, MR-guided LITT was performed with a percutaneous approach in a multiapplicator technique. Two temperature sensitive T1-weighted sequences (FLASH-2D- and TurboFLASH-sequences) were used to map the spatial and temporal distribution of Nd:YAG laser effects. Parallel fluoroptic temperature measurements were carried out by means of an inserted probe in a distance of 5-26 mm (mean: 14 mm) from the laser applicator. RESULTS: In both sequences a gradually increasing signal loss could be documented during laser application which proved to be reversible after cessation of energy deposition. the percentage of decrease in signal intensity correlated directly with the measured increase of temperature. Invasive fluoroptical evaluation of temperature distribution after 10 min exposure time showed at 5 mm distance from the applicator an increase of temperature of 35 degrees C, in 10 mm distance a mean increase of 9 degrees C +/- 1.7, in 15 mm a mean increase of 7 degrees C +/- 1.6 and in 20 mm a mean increase of 3 degrees C +/- 0.5. This is evidence of thermal tissue damage up to 3 cm in diameter with laser monoapplication. The qualitative evaluation revealed a reproducible correlation of the extent of signal loss around the applicator and the finally induced degree of necrosis. CONCLUSION: Invasive fluoroptical temperature measurements prove the diagnostic reliability of MR thermometry for the online monitoring of LITT of liver metastases.

Adult

[The diagnosis and imaging of the a. hepatica after orthoptic liver transplantation--a comparison of frequency-modulated and amplitude-modulated color Doppler sonography].

PURPOSE: We examined whether amplitude-modulated color Doppler (power Doppler) sonography provides a better anatomic imaging of the vascular course of the hepatic artery after liver transplantation. PATIENTS AND METHODS: 82 patients were examined with Doppler sonography after liver transplantation. The distal section of the hepatic artery was imaged both with frequency-modulated color Doppler (color Doppler) and power Doppler and a Doppler spectrum derived from each mode for determination of the flow velocity. RESULTS: Native imaging of the hepatic artery was possible in 78/82 patients, in 2/82 patients only after administration of Levovist, and in 2/82 patients it could not be seen. In these two patients the diagnosis of hepatic artery occlusion was confirmed by angiography. The anatomic course was demonstrated more longitudinally by power Doppler than by color Doppler (p < 0.001; chi 2 test) which made the angle correction easier. A disadvantage of power Doppler was the lack of image contrast to the portal veins; thus evaluation of the vascular course in this section was better possible with color Doppler by means of a specifically generated aliasing in the flow of the hepatic artery (p < 0.001; chi 2 test). Determination of the flow velocity showed no significant differences between color and power Doppler supported duplex sonography. CONCLUSIONS: The combined use of color Doppler and power Doppler improves visualization of the hepatic artery after liver transplantation. The lack of visualization of the vessel after administration of Levovist is diagnostic for occlusion of the vessel.

Adult