1 M Gd-chelate (gadobutrol) for multislice first-pass magnetic resonance myocardial perfusion imaging.

The aim of the study was to evaluate a 1 M gadolinium-chelate (gadobutrol) for first-pass MR myocardial perfusion examinations in patients with suspected coronary artery disease (CAD). In phantom studies, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values of gadobutrol were compared with gadopentetate (Gd-DTPA). 25 consecutive patients with clinically suspected CAD were examined with dynamic rest/stress MR perfusion examinations using 0.05 mmol kg(-1) gadobutrol. Semi-quantitative evaluation of the myocardial perfusion was performed by calculating the myocardial perfusion reserve index (MPRI). Hypoperfused regions were correlated with data from X-ray coronary angiography. In phantom studies, SNR/CNR of gadobutrol-doped blood samples were consistently higher for all applied flip angles at concentrations < or =1.0 mmol L(-1) compared with Gd-DTPA. Assessment of 81 stress perfusion series with gadobutrol in 25 patients yielded a sensitivity of 82% and specificity of 91% for significant CAD. Combining the information from all perfusion series of one patient yielded a sensitivity of 89% and specificity of 94% on a per-vessel basis. Gadobutrol exhibited favourable signal properties in phantom studies. Rest/stress myocardial perfusion examinations using 1 M gadobutrol yielded high sensitivity and specificity in detection of malperfused areas (82% and 91%, respectively). This is comparable with recently published perfusion data using 0.5 M Gd-DTPA.

[Radical cystectomy in the treatment of bladder cancer always in due time?]. / Stellen wir die Indikation zur radikalen Zystektomie immer zeitgerecht?

INTRODUCTION: The aim of this study was to examine how the survival rates for patients with muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 452 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2004. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n=114) patients who presented with a superficial bladder carcinoma which had a high likelihood of progressing underwent radical cystectomy. Group 2 included (n=92) patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n=246) comprised patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival rates and overall survival rates in the three groups were then compared. RESULTS: The average patient age at cystectomy was 64.3 (35-80) years, and the average follow-up period was 49 months. Progression-free survival and overall survival of all 452 patients were 56.1 and 53.6%, respectively, after 5 years. The best outcome was a progression-free 5-year survival rate of 78.4% with organ-confined, lymph node-negative tumors (n=213). This result was statistically significant (p<0.01) compared with the progression-free 5-year survival rate of 42.3% for non-organ-confined, lymph node-negative tumors (n=112). Lymph node-positive patients (n=127) achieved a progression-free 5-year survival rate of 29.0% regardless of the tumor infiltration. Group 1 patients achieved a progression-free survival rate of 71.3% and an overall survival rate of 69.1% after 5 years. Group 2 patients achieved a progression-free survival rate of 52.9% and an overall survival rate of 51.4% after 5 years. Group 3 patients achieved a progression-free survival and overall survival of 50.2% and 47.1%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p>0.45). However, both groups displayed significantly poorer progression-free and overall survival rates compared with group 1 (p<0.01). CONCLUSION: Our results show that patients with superficial bladder carcinoma with tumor progression to muscle invasion do not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out cystectomy. Due to these results we must expect that waiting for a muscle invasion in patients with superficial bladder carcinoma with a high risk profile results in a significant impairment of prognosis.

How far is the preoperative Kattan nomogram applicable for the prediction of recurrence after prostatectomy in patients presenting with PSA levels of more than 20 ng/ml? A validation study.

OBJECTIVE: We present an external validation study investigating the applicability of the preoperative Kattan nomogram for predicting recurrence after prostatectomy in a population of patients with serum prostate-specific antigen (PSA) levels exceeding 20 ng/ml. MATERIALS: In the evaluation of clinical parameters pooled from a total of 191 patients presenting with PSA levels ranging between 20.1 and 100 ng/ml, the PSA-free survival rate 60 months after surgery was calculated according to Kattan nomograms. Subsequently, the results were statistically compared with the corresponding actual survival rates obtained from Kaplan-Meier analysis. For this purpose, the patients were assigned to one of four different risk groups according to predictions derived from the Kattan nomograms, enabling a direct comparison of expected (as predicted by Kattan nomogram) versus actual survival of each patient investigated in our study. RESULTS: Predicted PSA-free survival rates were determined to be as follows: 83% (low risk group); 66% (intermediate risk group); 39% (intermediate-high risk group), and 10% (high risk group) in comparison with the actual survival rates determined to be 63, 62, 40 and 21%, respectively. For PSA levels ranging between 20.1 and 30 ng/ml, 30.1 and 50 ng/ml, and 50.1 and 100 ng/dl, PSA-free survival rates were found to be 57, 37, and 27% (p=0.0017), respectively, during a 5-year post-prostatectomy follow-up. CONCLUSIONS: The Kattan nomogram shows good statistical concordance with actual survival rates in the mean risk quadrants, but considerable differences were demonstrated concerning individuals with either a high or with a low risk of cancer progression.

[Differential diagnosis of focal liver lesions using contrast-enhanced MRI with SHU 555 A in comparison with unenhanced MRI and multidetector spiral-CT]. / Dignitätsbeurteilung fokaler Leberläsionen mit der kontrastverstärkten MRT mit SHU 555 A im Vergleich zur nativen MRT und zur Mehrzeilen-Detektor-Spiral-CT.

PURPOSE: To evaluate the ability of contrast-enhanced MRI with SHU 555 A to provide additional information for characterization of focal liver tumors compared with non-enhanced MRI and multislice spiral CT. MATERIALS AND METHODS: In a prospective manner the images of 45 patients who underwent multislice spiral CT, unenhanced MRI alone and unenhanced and SHU 555 A-enhanced MRI including dynamic imaging at a field strength of 1.0 T were analyzed in a blinded reading. The readers had to determine on a scale from 1 to 5 whether a tumor was benign or malignant. Furthermore, the readers had to give a definitive diagnosis for each lesion. A true cut needle biopsy served as gold standard against which all imaging procedures were compared. RESULTS: The sensitivity for differentiation malignant vs. benign lesion was 77 % with spiral CT, 72 % with unenhanced MRI and 94 % with SHU 555 A-enhanced MRI, respectively (p < 0.05). The specificity for spiral CT was 73 %, for unenhanced MRI 83 % and for contrast-enhanced MRI 83 %, respectively (n. s.). Compared with the histopathologic results, the correct diagnosis was made with spiral CT in 25/45 (56 %), unenhanced MRI in 16/45 (36 %) and contrast-enhanced MRI in 32/45 (71 %) of the patients (p < 0.05). For the subgroup of patients with liver cirrhosis, the correct diagnosis was established with spiral CT in 16/23 (70 %), unenhanced MRI in 9/23 (39 %) and contrast-enhanced MRI in 19/23 (83 %) of the patients (p < 0.05). CONCLUSION: Contrast-enhanced MRI with SHU 555 A has the ability to improve the differential diagnosis of focal liver tumors compared with unenhanced MRI and multislice spiral CT.

Significance of the time period between diagnosis of muscle invasion and radical cystectomy with regard to the prognosis of transitional cell carcinoma of the urothelium in the bladder.

OBJECTIVE: Standard treatment of muscle-infiltrated transitional cell carcinoma (TCC) of the urothelium consists of radical cystectomy. In some cases there is a delay between the initial diagnosis and a definitive treatment being administered. The objective of this study was to determine the effect of the time window between evidence of muscle invasion and radical cystectomy on the pathological stage and progression-free survival. MATERIAL AND METHODS: Between February 1992 and August 2002, 239 radical cystectomies were carried out as a result of TCC of the bladder. In a total of 189 patients (79%), cystectomy was carried out due to muscle-infiltrated TCC with no evidence of distant metastases (>/=T2, M0). The time between the diagnosis of muscle invasion and cystectomy was determined for all of these patients, who were then divided into two groups on the basis of a 3-month cut-off period. Univariate and multivariate analyses were used to determine the effect of the time period on clinical factors and progression-free survival. RESULTS: The average age of the patients was 63 (range 35-80) years. A median follow-up of 40 months showed a progression-free survival rate of 49% after 5 years. The average time between the diagnosis of muscle invasion and cystectomy was 1.8 (0.3-12.1) months. For a time window of >3 months, 30/42 patients (72%) showed signs of extravesical tumor growth and/or tumor-positive lymph nodes, compared to 89/147 patients (60%) (p = 0.198) for a time window of 3 months between diagnosis of muscle invasion and radical cystectomy were associated with an advanced pathological stage and a poorer progression-free survival. These results underline the need for early cystectomy within the 3-month period between diagnosis of muscle invasion and cystectomy.

Limited correlation between expansin gene expression and elongation growth rate.

The aim of this work was to study the role of the cell wall protein expansin in elongation growth. Expansins increase cell wall extensibility in vitro and are thought to be involved in cell elongation. Here, we studied the regulation of two tomato (Lycopersicon esculentum cv Moneymaker) expansin genes, LeExp2 and LeExp18, in rapidly expanding tissues. LeExp2 was strongly expressed in the elongation zone of hypocotyls and in the faster growing stem part during gravitropic stimulation. LeExp18 expression did not correlate with elongation growth. Exogenous application of hormones showed a substantial auxin-stimulation of LeExp2 mRNA in etiolated hypocotyls and a weaker auxin-stimulation of LeExp18 mRNA in stem tissue. Analysis of transcript accumulation revealed higher levels of LeExp2 and LeExp18 in light-treated, slow-growing tissue than in dark-treated, rapidly elongating tissue. Expansin protein levels and cell wall extension activities were similar in light- and dark-grown hypocotyl extracts. The results show a strong correlation between expansin gene expression and growth rate, but this correlation is not absolute. We conclude that elongation growth is likely to be controlled by expansin acting in concert with other factors that may limit growth under some physiological conditions.

Tarsal functions, movement, and stabilization mechanisms in foot, ankle, and leg performance.

The authors investigated the function of the tarsus and the skeletal segments of the foot in terms of the biomechanical significance of the individual links of the foot-ankle-leg complex. A performance model based on pressure-washed trabecular systems and the interface of the different segments making up the articular foot skeleton is presented and discussed. The biomechanical influence of these segments on each other and on their appendicular companion bones is assessed, and an explanation of their function is provided.

Pathophysiology in endothelin-1 transgenic mice.

Transgenic mice expressing the human endothelin-1 (ET-1) were generated. These mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension. Consequently, a progressive decrease in renal blood flow and/or glomerular filtration rate was observed, demonstrated by altered creatinine clearance and by magnetic resonance imaging. These genetically altered transgenic mice provide an interesting animal model in which to elucidate the role of ET-1 in the modulation of renal hemodynamics and glomerular and tubule functions.

[An interdisciplinary consensus conference on the diagnosis and therapy of testicular tumors]. / Interdisziplinäre Konsensus-Konferenz zur "Diagnostik und Therapie von Hodentumoren".

In 1988 the German testicular working group was set up by leading experts in the fields of urology, medical and radio-oncology. Since then, the working group has initiated several clinical studies and conferences with the aim of defining current standards in the treatment of testicular germ cell tumours. After a series of preliminary joint meetings with representatives from the AUO, AIO and ARO of the "Deutsche Krebsgesellschaft", a conference was held in May 1996 to agree on a consensus in diagnosis and treatment of testicular germ cell tumours. The standards which have been agreed on at the conference refer to the current international literature and provide recommendations for the majority of clinical situations. Treatment strategies differing from these standards should not be chosen except for well argued individual settings or patients treated in clinical trials. No consensus could be reached for nonseminomatous stage I, IIA and IIB tumours. As a consequence, the differing treatment strategies for these stages are summarized in this paper. A subsequent conference in later years is needed to possibly find an agreement for these tumour stages and to update the current standards according to new clinical experience and knowledge.

Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical profile of SH U555A.

RATIONALE AND OBJECTIVES: To evaluate the physical and pharmacological profiles of SH U555A, a suspension of magnetic iron oxide particles that is designed to enhance the visualization of liver tumors and metastases. MATERIAL AND METHODS: Chemical and physical methods were used to characterize the size and structure of these magnetic iron oxide particles in aqueous solution. The biodistribution and pharmacokinetics of the particles were studied in mice, rats and dogs. The imaging efficacy of the particles was demonstrated by MR imaging in rat liver tumors RESULTS: The SH U555A particles consist of low-molecular-weight carboxydextran-coated iron oxides predominantly of the gamma-Fe2O3 form with a hydrodynamic diameter ranging from 57-59 nm and strong T2 relaxivity of 164 liters x mmol(-1) x s(-1) (water, 0.47 T). In rats the particles exhibited a dose-dependent half-life of between 2 and 3 days in the liver at a dose of 20 micromol Fe/kg and a shorter half-life at lower doses. No major side effects were found. In a rat tumor model the tumor-to-liver contrast was markedly improved after i.v. administration of SH U555A. At a dose of 14 micromol Fe/kg the half-maximal contrast-effect was obtained even in nonoptimized T1-weighted spin-echo images. CONCLUSION: SH U555A is a superparamagnetic MR contrast agent for i.v. administration and has substantial potential for the demarcation of liver tumors.

Hepatic kinetics and magnetic resonance imaging of gadolinium-EOB-DTPA in dogs.

RATIONALE AND OBJECTIVES: To measure the hepatic uptake and biliary elimination kinetics of gadolinium (Gd)-EOB-DTPA in dogs. METHOD: Two groups of four beagles each were anesthetized and given an intravenous bolus of 25 mumol/kg or 250 mumol/kg of Gd-EOB-DTPA. Blood, hepatic bile, and urine were collected over 140 minutes, and liver samples were obtained immediately after the dogs were killed. Conventional T1-weighted spin echo sequences of the liver were performed on a 1.5-Tesla (T) magnetic resonance imager during sampling. A ninth beagle received a bolus of 25 mumol/kg followed 140 minutes later with a bolus of 250 mumol/kg of Gd-EOB-DTPA. Wedge liver biopsies were obtained for Gd estimation at various times after dosing, and Gd concentration was measured by inductively coupled plasma atomic emission spectroscopy. RESULTS: The plasma concentration of Gd-EOB-DTPA decreased in a biexponential manner with half-lives of approximately 4 minutes and 60 minutes for the distribution and elimination phase independent of the dose given. Gadolinium bile concentration reached peak values between 80 and 140 minutes: 6.3 +/- 1.6 mmol/L for the low dose (LD) and 11.6 +/- mmol/L for the high dose (HD). Bile Gd output was 62.0 +/- 8.8 (LD) and 78.3 +/- 30.2 (HD) nmol/minute-kg 50 to 80 minutes after injection. Gadolinium-EOB-DTPA was excreted by the biliary route to 24.8 +/- 2.6 (LD) and 3.6 +/- 1.2 (HD) percent of the dose within 140 minutes. Liver Gd concentration was 0.43 +/- 0.14 (LD) and 4.3 +/- 0.5 (HD) mmol/kg liver tissue at the conclusion of the studies. Calculated concentrations in the hepatocyte were 60 (LD) and 15 (HD) times higher than in plasma at 25 minutes after dosing. Whereas the low dose exhibited excellent contrast enhancement for the whole period, the high dose displayed a biphasic signal enhancement with a decreasing signal caused by the too-high hepatic gadolinium accumulation. CONCLUSIONS: Transport of the Gd-EOB-DTPA into the hepatocyte exceeded elimination from hepatocyte to bile. The high dose defined a biliary transport maximum for Gd-EOB-DTPA of 78.3 +/- 30.2 nmol/minute-kg. The liver accumulation results from fast transport into the hepatocyte and rate-limited slower transport from hepatocyte to bile. The accumulation occurs against a strong concentration gradient, suggesting energy-dependent active transport into the hepatocyte.

Anticorpo anti-Trypanosoma cruzi como fator de reatividade cruzada na pesquisa de anticorpos anti-DNA por imunofluorescência indireta / Anti-Trypanosoma cruzi antibodies as a factor of cross-reactivity in the research of anti-DNA antibodies by indirect immunofluorescence

Na pesquisa de anticorpos anti-DNA podem ser utilizadas várias metodologias como a imunofluorescência indireta (IFI), enzimaimunoensaio (ELISA) ou radioimunoensaio (RIE) com DNA marcado com 14C, sendo que a IFI empregando Crithçidia luciliae como substrato é a mais utilizada. Sendo este um parasita flagelado da família dos tripanosomatídeos, apresenta estruturas antigênicas comuns ao Trypanosoma cruzi. Portanto, soros de pacientes com sorologia positiva para Doença de Chagas (DC) podem apresentar uma reatividade cruzada entre estes parasitas, constituindo um fator interferente na reação de IFI para pesquisa de anticorpos anti-DNA. Com o objetivo de verficar a freqüência com que esta inferência ocorre na rotina laboratorial, analisou-se os resultados obtidos na pesquisa de anti-DNA por IFI realizadas no período de junho de 1994 a julho de 1995 no Setor de Imunologia Clínica do Hospital Universitário Regional do Norte do Paraná, Londrina-Paraná. Das 927 reações realizadas, 60 (6,47%) foram reagentes, 832 (89,75%) não reagentes e 35 (3,77%) apresentaram um padrão inespecífico de fluorescência. Suspeitando-se de reatividade cruzada, foram realizadas reações sorológicas para DC (HAI e IFI) nestas amostras, sendo que 100% apresentaram resultados reagentes para ambas as reações. Estes dados confirmam a interferência dos anticorpos anti-Trypanosoma cruzi na pesquisa de anticorpos anti-DNA por IFI e alertam para a necessidade da confirmação de resultados falsos-positivos, principalmente em regiões onde a DC é endêmica.

Pre-clinical evaluation of gadobutrol: a new, neutral, extracellular contrast agent for magnetic resonance imaging.

The Gd(3+)-complex of 10-(2,3-dihydroxy-1-hydroxymethylpropyl)-1,4,7,10-tetraazacyclo dodecane-1,4,7-triacetic acid(gadobutrol) is a new, neutral Gd-chelate for use as an extracellular contrast agent in magnetic resonance imaging (MRI). The blood level in dogs after intravenous (i.v.) injection decreased with a terminal half-life of about 45 min, the clearance was about 3.75 ml/min per kg and the distribution volume of 0.23 l/kg suggested an extracellular distribution. Biodistribution experiments in rats revealed that only a very small amount (0.16%) of the dose was left in the body 7 days after i.v. injection. Measurable amounts of Gd could be detected only in the liver, kidneys and bones. The osmolality (0.57 osmol/kg at 0.5 mol/l and 1.39 osmol/kg at 1 mol/l) is in the range of other low osmolality contrast media for MRI. Only very little interaction with biologically relevant molecules was suggested by a histamine release test and a lysozyme inhibition test. An i.v.-LD50 of 23 mmol/kg in mice combined with a comparatively high T1-relaxivity (5.6 l/mmol per s at 0.47 T and 6.1 l/mmol per s at 2 T) in plasma promises a high margin of safety. In preliminary imaging experiments, gadobutrol caused high enhancement in different lesions (cerebral infarct, brain tumor) of the rat. Tripling of the typical clinical dose of 0.1 mmol/kg was shown to provide additional diagnostic gain in lesions of this type.

Fifth metatarsal fractures. Biomechanics, classification, and treatment.

Fractures of the fifth metatarsal are treated conceptually based on anatomic location and character of the fracture site. Intra-articular disruptions require reconstruction, if possible. Malalignment of acute fractures requires either closed reduction or open reduction if the malalignment represents a load-bearing dysfunction to the forefoot. Segmental defects require bone grafting and stabilization with plate and screws. Jones fracture is most effectively managed with medullary lag screw delivery in the active or athletic patient. Casting can be considered for high-risk patients. Late bone grafting for sclerotic nonunion is necessary with inlaid grafts harvested from the calcaneus or tibia. Tuberosity fractures require open reduction only when articular involvement is a problem or when distraction is apparent. Otherwise, they can be expected to heal rapidly without long-term problems.

Early MR detection of experimentally induced cerebral ischemia using magnetic susceptibility contrast agents: comparison between gadopentetate dimeglumine and iron oxide particles.

PURPOSE: To evaluate early patterns of MR changes in a rat model of cerebral ischemia using the first pass of two magnetic susceptibility contrast agents. METHODS: One hours after endovascular middle cerebral artery occlusion, all animals were examined in an experimental MR unit. After bolus application of gadopentetate dimeglumine and, 10 minutes later, of iron oxide particles, the MR changes of the first pass of these contrast agents were followed using a T2*-weighted fast low-angle shot sequence. Time-density curves of both contrast agents were analyzed and compared. RESULTS: After bolus injection of either (paramagnetic) gadopentetate dimeglumine or superparamagnetic particles, nonischemic brain parenchyma decreased markedly in signal, whereas the ischemic brain area remained relatively hyperintense (and thus became clearly delineated). Only after application of gadopentetate dimeglumine did a mild reduction in signal occur in the ischemic hemisphere, although the main artery was occluded. An explantation for this phenomenon might be residual capillary perfusion (plasma flow), which is detectable only when the smaller (paramagnetic) contrast molecules are being used. CONCLUSIONS: Cerebral perfusion deficits can be detected 1 hour after vascular occlusion with T2*-weighted fast low-angle shot sequences and bolus injection of paramagnetic or superparamagnetic MR contrast agents. Gadopentetate dimeglumine may be used as a marker of microcirculatory plasma flow.

Anterior ankle impingement arthropathy. The role of anterolateral arthrotomy and arthroscopy.

The choice of anterior ankle arthroplasty conducted by anterolateral arthrotomy versus arthroscopic techniques depends on the severity of the osteophytosis and the dominance type. This can be determined in most cases by conventional radiology, contrast arthrography, or MRI. Diagnostic arthroscopy may be required when noninvasive means fail to provide the answer to anterior frontier joint pain. Thorough arthroplasty must be performed and the joint placed through its end range of motion to verify reduction of all impingements. Extensive bony impingements are most effectively treated by conventional anterolateral arthrotomy. This is particularly true in posttraumatic cases with considerable arthrofibrosis infiltrate. Lesser degrees of osteophytosis confined, in particular, to the leading tibial edge are effectively reduced by arthroscopic technique. Anterior ankle arthroplasty by either technique offers symptomatic relief of pain with minimal morbidity. It can serve as a definitive treatment protocol for many patients or simply represent a temporary step along the way to more aggressive salvage surgery such as arthrodesis.