Antiangiogenic tumor treatment: early noninvasive monitoring with USPIO-enhanced MR imaging in mice

PURPOSE: To prospectively investigate steady-state blood volume measurements for early quantitative monitoring of antiangiogenic treatment with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: The institutional animal care committee approved all experiments. HT-1080 fibrosarcoma-bearing nude mice were injected with a thrombogenic vascular targeting agent (VTA) (11 nude mice, 20 tumors) or saline (12 nude mice, 20 tumors). USPIO-enhanced (SH U 555C) MR imaging was performed after the VTA was administered. USPIO-induced changes in tissue R2* (DeltaR2*) were measured with a T2-weighted dual-echo echo-planar imaging sequence, and the vascular volume fraction (VVF) was calculated. Parametric DeltaR2* maps were analyzed with respect to tumor perfusion patterns. Correlative histologic analysis was performed for grading of tissue thrombosis, and tissue perfusion was quantified with fluorescent microbeads. Unpaired Student t test and Spearman nonparametric correlation coefficient were used for statistical analysis. RESULTS: The DeltaR2* values were significantly (P < .001) reduced shortly after treatment initiation (mean DeltaR2*, 0.017 msec(-1) +/- 0.0014 [standard error] in control animals vs 0.005 msec(-1) +/- 0.0007 in animals that received VTA), which was also reflected by a decrease in the VVF (2.47% +/- 0.18 vs 0.41% +/- 0.48, P < .001). Histologic analysis revealed various degrees of tumor thrombosis after VTA treatment that correlated inversely with the DeltaR2* values (r = -0.83). Moreover, tumor perfusion measurements corroborated the MR results, indicating a significant reduction in tissue perfusion after VTA treatment (mean tissue fluorescence, 570.4 arbitrary units [au] per gram +/- 27 vs 161.7 au/g +/- 17; P < .05). CONCLUSION: USPIO-enhanced MR imaging enables early monitoring of antiangiogenic treatment of tumors.     

R2 and R2* mapping for sensing cell-bound superparamagnetic nanoparticles: in vitro and murine in vivo testing

PURPOSE: To prospectively determine the cellular iron uptake by using R2 and R2* mapping with multiecho readout gradient-echo and spin-echo sequences. MATERIALS AND METHODS: All experiments were approved by the institutional animal care committee. Lung carcinoma cells were lipofected with superparamagnetic iron oxides (SPIOs). Agarose gel phantoms containing (a) 1 x 10(5) CCL-185 cells per milliliter of agarose gel with increasing SPIO load (0.01-5.00 mg of iron per milliliter in the medium), (b) different amounts (5.0 x 10(3) to 2.5 x 10(5) cells per milliliter of agarose gel) of identically loaded cells, and (c) free (non-cell-bound) SPIOs at the iron concentrations described for (b) were analyzed with 3.0-T R2 and R2* relaxometry. Iron uptake was analyzed with light microscopy, quantified with atomic emission spectroscopy (AES), and compared with MR data. For in vivo relaxometry, agarose gel pellets containing SPIO-labeled cells, free SPIO, unlabeled control cells, and pure agarose gel were injected into three nude mice each. Linear and nonlinear regression analyses were performed. RESULTS: Light microscopy and AES revealed efficient SPIO particle uptake (mean uptake: 0.22 pg of iron per cell +/- 0.1 [standard deviation] for unlabeled cells, 31.17 pg of iron per cell +/- 4.63 for cells incubated with 0.5 mg/mL iron). R2 and R2* values were linearly correlated with cellular iron load, number of iron-loaded cells, and content of freely dissolved iron (r(2) range, 0.92-0.99; P < .001). For cell-bound SPIO, R2* effects were significantly greater than R2 effects (P < .01); for free SPIO, R2 and R2* effects were similar. In vivo relaxometry enabled accurate prediction of the number of labeled cells. R2' (R2* - R2) mapping enabled differentiation between cell-bound and free iron in vitro and in vivo. CONCLUSION: Quantitative R2 and R2* mapping enables noninvasive estimations of cellular iron load and number of iron-labeled cells. Cell-bound SPIOs can be differentiated from free SPIOs with R2' imaging.     

Fracture consolidation in a tibial nonunion after revascularization: a case report

Poor vascularity can be a potential contributor in the development of fracture nonunion. There is little evidence in orthopaedic literature suggesting that poor vascularity alone may lead to the development of nonunion. Experimental models addressing the effects of ischemia on fracture healing have yielded conflicting views. The case presented here describes a patient who sustained a Type IIIC tibial shaft fracture requiring vascular repair and soft tissue coverage. The patient developed an aseptic, atrophic nonunion. In preparation for operative management of her nonunion, the patient underwent angioplasty in the lower extremity for stenotic vessels. Shortly thereafter, the patient's nonunion went on to unite with no additional intervention, suggesting that revascularization alone resulted in this dramatic progress to union. Further prospective clinical studies may reveal a role for the use of vascular evaluation and intervention in the diagnosis and treatment of nonunion.     

Does morbid obesity negatively affect the hospital course of patients undergoing treatment of closed, lower-extremity diaphyseal long-bone fractures?

Obesity is prevalent in the developed world and is associated with significant costs to the health care system. The effect of morbid obesity in patients operatively treated for long-bone fractures of the lower extremity is largely unknown. The National Trauma Data Bank was accessed to determine if morbidly obese patients (body mass index >40) with lower extremity fractures have longer length of hospital stay, higher cost, greater rehabilitation admission rates, and more complications than nonobese patients. We identified patients with operatively treated diaphyseal femur (6920) and tibia (5190) fractures. Polytrauma patients and patients younger than 16 years were excluded. Morbidly obese patients were identified by ICD-9 and database comorbidity designation (femur, 131 morbidly obese; tibia, 75 morbidly obese). Patients meeting these criteria who were not morbidly obese were used as controls. Sensitivity analyses were performed to analyze patients with isolated trauma to the tibia or femur. Morbidly obese patients were more likely to be admitted to a subacute facility. Length of stay trended higher in morbidly obese patients. There was no significant relationship between obesity and inpatient mortality or inpatient complications. These trends held true when considering patients with multiple injuries and patients who had isolated long-bone injuries. Our study showed that morbidly obese patients may have greater rehabilitation needs following long-bone fractures in the lower extremity. Our study showed no difference in mortality or complications, although further studies are needed to confirm these findings.     

The vehaviour of monoaminooxydase (MAO) activity in tumours. I. MAO activity measurement in experimental tumours (author's transl)]

The activity of MAO (EC 1.4.3.4) was measured in liver homogenates of mice with experimental tumours Sarcoma S-180 and Leukemia L-1210. The enzyme activity was determined by two methods: spectrophotometric--with benzylamine as a substrate and the second with the application of oxygen electrode and adrenaline as a substrate. An increase of the enzyme activity was observed in liver homogenates of mice with Sarcoma S-180 as compared with the controls. High activity of MAO with both substrates was also observed in Sarcoma ascites. In Leukemia L-1210 changes of activity in relation to adrenaline as a substrate were very small, but towards benzylamine the affinity of enzyme was higher (the increase of activity was about 50%).     

Composite antebrachial island flap]

Two cases of antebrachial island flap including the radial bone have been presented. In the first patient it was used to fill infected defect of skin and the 2nd metacarpal bone. In the second patient, the operation was indicated by shortening (2 cm) of the 3rd metacarpal bone after its intraarticular fracture. In both patients, the bone and skin grafts healed.     

Über absteigende Hinterstrangsdegeneration

Ohne ZusammenfassungHierzu Taf. I und II.     

Laparoscopic treatment of parapubic postprostatectomy hernia.

We are reporting the case of a parapubic hernia that occurred after radical prostatectomy. This kind of the hernia is caused by the weakening of the attachments of rectus muscles to the pubic bone. Because of its location, it may be misdiagnosed as a far more common direct inguinal hernia. A laparoscopic approach made it possible to precisely diagnose and repair the defect in the abdominal wall.