Biomedical subjects

Reinhard Vonthein

Publications and source records attributed to Reinhard Vonthein.

At least 19 recordsLinked to original sources

PubMed2007

Prospective comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced malignant melanoma.

The aim of our study was to compare the overall and site-based accuracy and impact on patient management of positron emission tomography/computed tomography (PET/CT) and whole-body (wb) magnetic resonance imaging (MRI) in staging of advanced melanoma. In a prospective blinded study, 64 patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma underwent 18F-fluorodeoxyglucose PET/CT and wbMRI. In total 420 lesions were evaluated. The overall accuracy of PET/CT was 86.7% compared to 78.8% for wbMRI (P=0.0007). PET/CT was significantly more accurate in N-staging and detecting of skin and subcutaneous metastases, whereas wbMRI was more sensitive in detecting liver, bone and brain metastases. WbMRI was less sensitive but more specific than PET/CT in classifying pulmonary lesions. In 41 patients (64%) whole-body imaging caused changes of treatment. Whole-body staging of patients with advanced melanoma is most accurate by combining wbPET/CT and organ-specific wbMRI including a brain, liver and bone marrow protocol.

Adult↗

PubMed2006

Clinical efficacy and cognitive side effects of bifrontal versus right unilateral electroconvulsive therapy (ECT): a short-term randomised controlled trial in pharmaco-resistant major depression.

BACKGROUND: In most studies right unilateral electroconvulsive therapy (ECT) has been shown to cause fewer cognitive side effects but less antidepressant efficacy compared with bi(fronto)temporal ECT at certain intensities. AIMS: To compare the short-term efficacy and side effects of right unilateral ECT and bifrontal ECT. METHODS: In a double-blind randomised controlled clinical trial, 92 patients diagnosed with pharmaco-resistant major depression received either six right unilateral ECT treatments (250% stimulus intensity of titrated threshold) or six bifrontal ECT (150% of threshold) treatments over a 3-week period. Concomitant psychotropic medications were continued during ECT treatments. The severity of depression and cognitive status was assessed prior to the first ECT and one day after the sixth ECT using the 21-item Hamilton Depression Rating Scale and the modified Mini Mental State Examination. RESULTS: Eight patients did not complete the course of the study due to minor side effects or withdrawal of consent. The mean Hamilton Depression score decreased from 27 to 17 points in both groups of 46 patients, resulting in 12 responders (primary endpoint defined as a decrease >50%) in each patient group (95% confidence interval for the odds ratio from 0.35 to 2.8). There was no reduction in the modified Mini Mental State score (mean score 86 of 100 points). CONCLUSIONS: Both bifrontal and right unilateral electrode placements in ECT were reasonably safe and moderately efficacious in reducing symptoms of pharmaco-resistant major depression.

Adult↗

PubMed2006

Added value of SPECT/CT in patients suspected of having bone infection: preliminary results.

AIM: We evaluated the contribution of SPECT/CT as an adjunct to combined three-phase bone scintigraphy (planar and SPECT) for diagnosing and localizing bone infection. Subsequently, the diagnostic performance of SPECT/CT was compared to visual fusion of SPECT with data of additional CT, X-ray, or MRI studies (SPECT + CT/X-ray/MRI). MATERIALS AND METHODS: Thirty-one patients suspected of bone infection, presenting pathological findings on triple-phase bone scintigraphy, underwent additional SPECT/CT. The SPECT/CT-technology combines the acquisition of SPECT and CT data with the same imaging device enabling perfect overlay of anatomical and functional images. (99m)Tc-DPD was used as radiopharmaceutical in all patients. For data analysis findings of bone scintigraphy (planar scans as well as SPECT) were categorized as positive, negative, or equivocal for the presence of osteomyelitis. In a second step, they were compared with SPECT/CT and SPECT + CT/X-ray/MRI with respect to localization and classification of lesions. Validation was achieved by surgery, biopsy, or by clinical follow up over at least 9 months including microbiological and radiological findings. RESULTS: Three-phase bone scan (incl. SPECT) correctly classified 7 lesions as positive and 11 lesions as negative for osteomyelitis. Six scans were interpreted false positive, two false negative, and five as equivocal. Rating the latter as positive for osteomyelitis, sensitivity of bone scan was (78%), specificity (50%). SPECT/CT was true positive in 7 patients, and true negative in 19. There were two false positive and two false negative findings, one scan was equivocal (sensitivity 78%, specificity 86%). Definition of anatomical localization of inflammatory foci was much easier by SPECT/CT due to better depiction of underlying anatomical details. SPECT + CT/X-ray/MRI yielded the highest sensitivity (100% compared to 78% of SPECT/CT), if equivocal findings (5/31 compared to 1/31 for SPECT/CT) are rated as true positive for osteomyelitis. Among radiological techniques, MRI (2 x FP) and CT (2 x FN) proved equal and expectedly superior to X-ray in delivering the correct diagnosis. CONCLUSION: SPECT/CT improves the diagnostic performance of three-phase bone scan for osteomyelitis by avoiding false positive or equivocal results. An additional benefit over visual fusion of SPECT with X-ray, CT, or MRI studies could not be confirmed in our study.

Adult↗

PubMed2006

Solitary pulmonary nodules: association between signal characteristics in dynamic contrast enhanced MRI and tumor angiogenesis.

PURPOSE: To estimate the association between signal characteristic of dynamic enhanced MRI using curve types and angiogenesis in solitary pulmonary nodules. MATERIALS AND METHODS: Thirty-six patients with a solitary pulmonary nodule (SPN) ranging in size from 6 to 37 mm (median 17 mm) underwent dynamic contrast enhanced MRI with a time interval of 10 s over a total period of 4 min. Resulting from the time-intensity curves four different enhancement curve profiles (A-D) were defined: type A with strong increase followed by early washout, type B with strong increase without washout, type C with slow increase and type D without relevant increase. Maximum peak (Pmax), slope of the first bolus transit (slope) and washout were calculated. Microvessel densities (MVD) were counted at the margins and at the center of the nodules. The mean MVD of each nodule was calculated. Enhancement characteristics were correlated with MVD grouped by diagnosis and by curve types. Curve types were correlated with the score of vascular endothelial growth factor (VEGF). RESULTS: The frequency of malignancy was 55% (20/36). Using curve types for differentiation between malignant and benign SPN, the sensitivity, specificity and accuracy were 100%, 75% and 89%, respectively. The correlation between Pmax and MVD(mean) for all nodules was moderate (r(s)=0.4, P=0.02). A relevant correlation was found between Pmax and MVD(margin) in curve type A (r(s)=0.63; P=0.04) and Pmax and MVD(mean) in curve type C (r(s)=0.86; P=0.006). No positive correlation was found between Pmax and MVD (mean, center and margin) in curve type B. No significant correlation was found for slope and washout. VEGF score correlated positively with curve types (r(s)=0.67; P<0.001). CONCLUSION: A relevant association between perfusion curve profiles and angiogenesis was found in malignant nodules having early washout and in benign lesion with a slow increase of enhancement. In cases of strong signal increase without washout additional factors for enhancement must be considered. The use of curve profiles could allow for the estimation of the extent of VEGF.

Adenocarcinoma↗

PubMed2006

Cross-chest median nerve transfer: a new model for the evaluation of nerve regeneration across a 40 mm gap in the rat.

A new animal model for the study of nerve regeneration in rats across a 40 mm gap between both median nerves is described. For autologous grafting, the ulnar nerves were dissected and sutured together. From the left median nerve, they were transplanted across the chest to the right median nerve. Animals having undergone this operation were observed for 12 months and periodically assessed using the grasping test and measurements of body-weight. For histological analysis rats were sacrificed after this period and axon counts were determined at the suture points of operated animals and in the median nerve of non-operated animals. Functional recovery could be seen, although partially, beginning as early as the fifth postoperative month, as demonstrated by the grasping test. Quantification of the number of axons demonstrated axonal regeneration across all three coaptation points. This model provides a new approach for analysis of long distance peripheral nerve regeneration without impairment of behaviour.

Animals↗

PubMed2006

Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children.

Recombinant human deoxyribonuclease I (dornase alfa) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis. In a randomized, placebo-controlled, double-blind clinical study in 100 infants, we investigated whether the therapeutic use of dornase alfa can be extended to ventilated, fluid-restricted children to reduce reintubation rate, ventilation duration, pediatric intensive care unit (PICU) stay, and ventilation complications. While reintubation rates were similar for dornase alfa 7% vs. placebo 9% (odds ratio, 0.77; confidence interval, 0.11-4.9), the incidence of atelectasis (6 vs. 17, respectively; P-value 0.051), median ventilation time (2.2 vs. 3.4 days, respectively; P-value 0.043), median length of PICU stay (7 vs. 8 days, respectively; P-value 0.051), and mean costs (4,830 vs. 6,320, respectively) were lower in the dornase alfa group. No adverse effects were observed, even in critically ill patients. We found that dornase alfa was beneficial and safe. Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward, particularly when longer ventilation (>3 days) is expected in fluid-restricted children after cardiac surgery.

Administration, Inhalation↗

PubMed2006

The polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene is not associated with the diagnosis of alcoholism or alcohol withdrawal seizures.

As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor, the genes encoding for the GABAB receptor can be considered as candidate genes for alcoholism and alcohol withdrawal seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene had been associated with alcoholism and EEG abnormalities in prior studies, the present examination investigated if the polymorphism is associated with the diagnosis of alcoholism or AWS. After genotyping the allele and genotype frequencies of a group of alcoholics with a history of AWS (n = 69) were compared with the results of a group of alcoholics with only mild withdrawal symptoms (n = 97). Additionally a group of healthy controls (n = 101) was compared with individuals with the diagnosis of alcoholism (n = 220). As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.

Adult↗

PubMed2006

Atrial linear lesions: feasibility using cryoablation.

BACKGROUND: Long linear lesions are created in the left atrium to modify the atrial substrate, thereby curing atrial fibrillation. The creation of long linear left atrial lesions using radiofrequency (RF) ablation is time consuming and difficult. Furthermore, it might result in significant complications. Cryoablation might overcome some of the disadvantages of RF ablation. Therefore, the aim of our study was to assess whether the creation of a long linear lesion is possible using cryotherapy. METHODS: A right atrial septal linear lesion was created in six pigs (median weight: 50 kg; range: 40-60 kg). The ablation procedure was performed with a 7-F Freezor cryocatheter. The nonfluoroscopic mapping system LocaLisa was used as a navigation tool. At each point, freezing was maintained at the lowest attainable temperature (-75 degrees C) for 4 minutes. The CARTO system was used for the evaluation of the linear lesions. Furthermore, all animals were sacrificed immediately after the ablation procedure and a postmortem examination of the lesions was performed. Additionally, an analysis of the amplitudes of the intracardiac electrograms registered via the ablation catheter was performed before and after the ablation procedure. RESULTS: A right atrial septal linear lesion could be created successfully in all six pigs. For the performance of this ablation line, a median number of 16 cryoapplications (range, 11-26) was necessary. The amplitudes of the intracardiac electrograms registered via the ablation catheter decreased significantly after ablation. The CARTO bipolar voltage map revealed very low potentials along the ablation line and showed a sharply demarcated ablation area at the septum in all pigs. Further analysis of the CARTO map revealed an incomplete conduction block in all cases. Most of the pigs had a small gap close to the fossa ovalis. The postmortem examination of 2,3,5-triphenyl-tetrazolium chloride-stained specimens showed sharply demarcated lesions without any ulcerations. There were no major complications during the procedure. CONCLUSIONS: The creation of long linear lesions using cryoablation is feasible and safe. Lesion characteristics are different and more favorable than those created by RF. However, the aim of creating a transmural lesion and a complete conduction block remains an unsolved problem even with current cryoablation techniques. Nevertheless, growing experience and technical improvements might overcome some of the current limitations of this new technique.

Animals↗

PubMed2006

Scotoma mapping by semi-automated kinetic perimetry: the effects of stimulus properties and the speed of subjects' responses.

PURPOSE: The study aimed firstly to determine the effects of stimulus variables on the detection of a scotoma border and, secondly, to study the reproducibility of the method during semi-automated kinetic perimetry. METHODS: The size of the physiological blind spot in 18 young normal subjects was measured with a video-campimetric device, the Tübingen computer campimeter (TCC). Kinetic stimuli of two different sizes and at four different levels of luminance were presented. Examinations were repeated within 2 weeks. Measurements were corrected for individual response times and the area of the blind spot was computed. The effects of stimulus strength and size and the repeatability of blind spot measurements were evaluated by an analysis of variance. RESULTS: The physiological blind spot showed significant inter- and intraindividual variations in size (least square means ranging from 17 to 49 square degrees), with a standard deviation of 6.8 square degrees. The measured size of the blind spot increased as a function of decreasing stimulus value, by reducing either the relative brightness or the size of stimuli. Use of a correction for each subject's speed of responses nearly halved the level of random variance. The temporal sequence of measurements (the order in which they were performed) had no apparent effect on the calculated values of blind spot size. CONCLUSIONS: Semi-automated kinetic perimetry can determine the size of the physiological blind spot with good repeatability in young, normal subjects. Determination of each individual's speed of response and inclusion of this variable in the calculations reduced variance of the measure significantly. This study confirmed the presence of considerable interindividual differences in the size of the physiological blind spot.

Adult↗

PubMed2006

Cytomegalovirus pneumonia after stem cell transplantation: correlation of CT findings with clinical outcome in 30 patients.

OBJECTIVE: The purpose of our study was to assess the correlation between early high-resolution CT findings of cytomegalovirus (CMV) pneumonia in patients with blood disorders and their clinical outcomes. CONCLUSION: The initial high-resolution CT findings in immunocompromised patients with CMV pneumonia seem to predict the patient's outcome being unfavorable in those forms of disease beginning mostly bilaterally as diffuse or patchy ground-glass opacity followed by progressive air-space consolidation. Also, a change in the CT morphology of pulmonary lesions toward diffuse ground-glass opacity seems to correlate with an unfavorable disease course.

Adult↗

PubMed2006

Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome.

OBJECTIVE: The aim of this study was to assess CT signs of invasive pulmonary aspergillosis (IPA) and their long-term kinetics in correlation with clinical findings and outcome. MATERIALS AND METHODS: Three hundred ten serial CT scans (mean, 7.7) in 40 consecutive patients were reviewed retrospectively over a median follow-up of 112 days (range, 5-841 days). Along with underlying disease, hematopoietic stem cell transplantation, neutropenia, graft-versus-host disease or antifungal treatment, signs of IPA, and number or size of lesions were evaluated regarding outcome and radiologic dynamics. RESULTS: On the day of IPA diagnosis, median lesion number and size were 3 or 3.1 cm(2), respectively. Irrespective of antifungal therapy, 90% of patients showed an increase in lesion size and number until day 9 (median and mean). Lesion size subsequently showed a median plateau phase of 3.5 days (mean, 7), during which median lesion numbers dropped by 17%. Consequently, 42.5% of patients showed a complete radiologic remission within a median 80 days. Of all parameters, formation of cavitation most strongly predicted time until radiologic remission, which was 2.5 times as long in patients with cavitary lesions. Likewise, cavitations were strong precursors of beneficial outcome (odds ratio, 8.4; confidence interval [CI], 1.07-176). CONCLUSION: The kinetics of radiologic signs of IPA adheres to a distinctive pattern with initial rise in number and size, followed by a plateau phase of size and gradual reduction. Both time until complete radiologic remission and outcome are independent of initial or maximum lesion size and number yet strongly influenced by cavitation.

Adolescent↗

PubMed2005

Bifunctional chimeric SuperCD suicide gene -YCD: YUPRT fusion is highly effective in a rat hepatoma model.

AIM: To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS: To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC), we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase (YCD) and the yeast uracil phosphoribosyltransferase (YUPRT) gene. RESULTS: In vitro stably transduced Morris rat hepatoma cells (MH) expressing the bifunctional SuperCD suicide gene (MH SuperCD) showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH cells stably expressing YCD solely (MH YCD) or the cytosine deaminase gene of bacterial origin (MH BCD), respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions (P<0.01) under both high dose as well as low dose systemic 5-FC application, whereas MH tumors without transgene expression (MH naive) showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness (SuperCD>> YCD>>BCD>>>negative control) was defined as a result of a direct in vivo comparison of all three suicide genes. CONCLUSION: Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model, thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.

Animals↗

PubMed2005

Quantification of stato-kinetic dissociation by semi-automated perimetry.

The difference in threshold sensitivities that are found when examining the visual field (VF) with static versus kinetic perimetric methods is called stato-kinetic dissociation (SKD). In this pilot study, we describe a semi-automated procedure for quantifying SKD. Fifteen patients with VF defects were examined with kinetic and static perimetry. SKD values were defined as positive when the static scotoma was larger than the kinetic one. We found significant local variations of SKD along scotoma borders with the individual reaction time as an important criterion when determining kinetic thresholds. There was a verifiable SKD in all patients with locally negative values in eight subjects.

Adult↗

PubMed2005

CNS involvement occurs more frequently in patients with Behçet's disease under cyclosporin A (CSA) than under other medications--results of a retrospective analysis of 117 cases.

The aim of this study was to evaluate the incidence of neurological manifestations of Behçet's disease (BD) in patients on cyclosporin A (CSA) compared with those on other medications. The records of 117 patients with BD who visited our hospital between 1990 and 2003 were reviewed with respect to symptoms and medication. All episodes of constant therapy prior to central nervous system (CNS) involvement were counted, and then the associations were analysed by the exact Fisher-Freeman-Halton test and adjusted for multiple tests by the Bonferroni-Holm method. We observed ten new cases of CNS manifestations in our patients with BD being regularly seen and treated in our tertiary care centre. The overall prevalence of neuro-BD in our patient group was 8.5%. In a retrospective analysis, the incidence of new-onset neurological disease (neuro-BD) in all patients with BD who regularly visited our hospital was significantly higher in patients on CSA than in those on other medications (6 of 21 vs 0 of 175 episodes, P<0.0001). This contrasts the obvious efficacy of CSA on extracerebral manifestations of BD, such as severe ocular disease, mucocutaneous lesions or arthritis. CSA exerts differential efficacy on various manifestations of BD. It is very effective for severe ocular and other moderate to severe manifestations of BD, but its efficacy for the prevention of neuro-BD seems to be inferior to that of other medications used in BD, such as azathioprine or interferon-alpha. The reasons for this are unclear, but the potential toxic effects of CSA on the CNS may be a predisposing factor for CNS vasculitis in BD.

Adolescent↗

PubMed2005

Pupil size and Perimetry--a pharmacological model using increment and decrement stimuli.

BACKGROUND: To assess the influence of natural and pharmacologically induced pupil size fluctuations on differential luminance sensitivity threshold (DLS) using bright (increment) and dark (decrement) stimuli. METHODS: Twelve healthy volunteers (20-30 years) were examined under the effect of phenylephrine 2%, dapiprazole 0.5%, and placebo. Pupil size was recorded by infra-red video camera in sessions without and with visual field examination (Tübingen Computer Campimeter). DLS was estimated at 9 locations within the central 20 degrees visual field, using bright and dark 26 min-of-arc-stimuli (10 cd/m(2) background, 4-2-1 dB thresholding strategy, four reversals). RESULTS: There were substantial inter-individual differences in pupil size and pupil size fluctuations. Intra-individual differences were small. Independently of medication, pupil size fluctuations were reduced by more than one-third when a subject was undergoing perimetric examination. Pupil size affected DLS on its own (slope 0.21 dB/mm; 95% CI: 0.09-0.33 dB/mm), differently at different stimulus locations, and to a greater extent with increment than with decrement stimuli (slope difference 0.13 dB/mm; 95% CI: 0.00-0.26 dB/mm). CONCLUSIONS: Campimetric examinations have a stabilising effect on pupil size fluctuations. Pupil size affects DLS with bright stimuli more than with dark stimuli; in normal young subjects this effect is not relevant for clinical or normative studies.

Adrenergic alpha-Agonists↗

PubMed2005

Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

PURPOSE: To assess early high-resolution computer tomographic (CT) signs of invasive pulmonary aspergillosis (IPA) in non-HIV immunosuppressed patients and their potential association with patient's outcome, including frequency and severity of pulmonary hemorrhage, taking also in consideration the impact of other known risk factors contributory to IPA. MATERIAL AND METHODS: A retrospective review of serial CT scans was performed in 45 immunocompromised patients with a total of 46 episodes of invasive pulmonary aspergillosis. All patients underwent CT beginning with the day they showed clinical or laboratory signs of infection. Serial follow-up CT included more than two, up to 12 CT examinations. Patient's outcome was judged by clinical and radiological follow-up and classified as survival, death by IPA, or death unrelated to IPA. The influence of patient's age, underlying disease, hematopoietic stem cell transplantation, neutropenia, graft versus host disease, and antifungal therapy onset was also statistically considered. RESULTS: Three main CT findings were identified: small nodules (<1cm) 43% (20/46), large nodules 21% (10/46) and consolidations, either in patchy+/-segmental 26% (12/46), or peribronchial distribution+/-tree in bud 9% (4/46). In 11 patients (24%) we found a combination of two or more of these signs: 9 (19%) patients presented concurrent small nodules accompanied by reticulation, tree in bud or peribronchial infiltrates, while 2 (4%) patients showed large pulmonary nodules accompanied by large consolidations. An accompanying "halo" sign was observed in 38 patients (82%). Crescent sign followed by cavitation was encountered in 29 patients (63%). Two patients succumbed to massive pulmonary bleeding caused by IPA. Twenty-one patients (15/46) deceased in this series, 12 of them succumbed to IPA, 1 died from cerebral invasive aspergillosis, while in 9 patients the cause of death was not primarily IPA. Manifest pulmonary hemorrhage occurred in 19% (9/46) of IPA episodes. CONCLUSION: Initial CT findings of invasive pulmonary aspergillosis consist mainly of small nodules or patchy consolidations, showing in 82% of cases an early halo sign. Serious pulmonary hemorrhage was an infrequent clinical complication in our series, with an attributable mortality of 4.3%. IPA-related lethality was 26%, in our cohort. None of the early HRCT signs seemed to predict outcome.

Adolescent↗

PubMed2005

Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC.

Hepatocellular carcinoma (HCC) is regarded as a suitable target for antiangiogenic strategies. However, antiangiogenic agents aimed at single targets can be neutralized by upregulation of other proangiogenic factors. Therefore, combined approaches addressing at least two angiogenic targets should be more effective. Employing an appropriate rat hepatoma model, we examined the effects of sFlt-1 (soluble vascular endothelial growth factor [VEGF] receptor 1 as an indirect inhibitor of angiogenesis) and endostatin (a direct inhibitor of angiogenesis) in both single-agent as well as combined approaches under in vitro and in vivo conditions. Similar to human HCC, rat Morris hepatoma (MH) cells secreted high levels of VEGF, but no endogenous sFlt-1. Parental MH or MHES(r) cells, stably expressing rat endostatin, were adenovirally transduced either with AdsFlt-1 (encoding sFlt-1) or control vector Adnull (containing no transgene), followed by subcutaneous inoculation into syngeneic ACI rats. Compared with MH/Adnull cells, expressing no antiangiogenic factors at all, tumor weights were reduced fourfold in the MHES(r)/Adnull group, 19-fold in the MH/AdsFlt-1-group, and 77-fold in the MHES(r)/AdsFlt-1 combination therapy group. Analysis of variance did not show a significant interaction between the effects of the two factors ES(r) and sFlt-1; their effects multiplied. In conclusion, combined expression of sFlt-1 and endostatin effectively suppresses HCC growth under in vivo conditions. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Angiogenesis Inhibitors↗

PubMed2005

Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography.

OBJECTIVE: The goal of this study was to establish the feasibility of a low-dose whole-body multidetector row-CT (MDCT) protocol in the diagnosis of multiple myeloma (MM), as an alternative to conventional X-ray imaging, which is currently still state-of-the-art in these patients, with emphasis on the comparison of image resolution on axial and multiplanar reformatted (MPR) scans and reduction of radiation dose. MATERIAL AND METHODS: 100 patients with known MM, or monoclonal gammopathy of unknown significance (MGUS) underwent unenhanced whole-body MDCT on a 16-slice scanner in a randomised fashion, using a 16 x 1.5 mm collimation and four different energy parameters (40, 50, 60 and 70 mAs). Three different reconstruction algorithms were used in every patient (B40f, B50f and B60f kernel). CT scans were reviewed independently by two radiologists, with regard to correct classification into one of the three known MM stages, and recognition of fracture risk. Thereafter, axial and MPR images were evaluated in consensus by both readers, with respect to image resolution. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done only on MPR images. The distribution of image resolution categories (very good, good, sufficient, insufficient for diagnosis) was evaluated depending on following parameters: current time product, patient's weight, bone density and reconstruction algorithm. The effective radiation dose was determined with the aid of an anthropomorphic Alderson Rando-Phantom, using a tube current time product of 40 mAs, and then extrapolating it on all current time products applied in this study on a commercially available software program WinDose (Institute of Medical Physics, Erlangen, Germany). RESULTS: In all 100 patients, image resolution was diagnostic, regardless of scanning parameters, enabling correct classification of multiple myeloma patients. Image quality of MPR images was either equal or inferior to correspondent axial images in the delineation of smaller lytic lesions, because of the use of non-isotropic voxel size. However, they proved accurate in diagnosing fracture and spine misalignment. A strong dependency of image resolution on bone density was observed, with reduced quality in patients with either diffuse skeleton infiltration or concurrent osteoporosis. Spatial resolution was also dependent on the reconstruction algorithm and energy level (mAs) used, as well as on patient's weight, but their influence was low within the given ranges. A middle-frequency reconstruction algorithm (B50f kernel) proved beneficial for all energy protocols. The interobserver agreement was excellent (kappa = 0.95) for classification of MM-patients. Effective radiation dose of MDCT calculated at a tube current time product of 40 mAs was 1.7-fold higher than the mean radiation dose of conventional X-ray (4.1 mSv versus 2.4 mSv). DISCUSSION: Our study shows that whole-body low-dose MDCT investigational protocols are appropriate for the diagnosis of lytic bone changes and for assessment of fracture risk in multiple myeloma patients, representing a serious alternative to current standards.

Aged↗