An 8-year-old boy with vertebral artery dissection with cerebellar ataxia featuring suspected vertebral artery hypoplasia

We report an 8-year-old boy with left vertebral artery dissection featuring cerebellar ataxia in which congenital vertebral artery hypoplasia was suspected as a predisposing factor in the dissection. The patient suddenly suffered from vertigo and vomiting while swimming, and he was brought to our department. The initial brain Computed Tomography (CT) demonstrated no abnormalities, and his symptoms disappeared the next morning. However, one month after onset, brain Magnetic Resonance Imaging (MRI) revealed ischemic changes (infarction) in the left cerebellum. Transfemoral angiography showed complete occlusion at the C2 portion of the left vertebral artery, suggesting dissection and diffuse narrowing of the proximal segment of the occlusion site. Three-dimensional CT angiography also revealed diffuse narrowing of the left vertebral artery from the bifurcation of the subclavian artery. He has since been living daily life without any difficulties. The detailed etiology of cerebral artery dissection remains unknown, but arterial anomalies should be considered as a predisposing factor.     

Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects

We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha (pegIFN-alpha) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-alpha plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the Montgomery-Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone-substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. CONCLUSION: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-alpha and ribavirin.     

Influence of attenuation correction by integrated low-dose CT on somatostatin receptor SPECT

AIM: Somatostatin receptor scintigraphy (SRS) is well-established in neuroendocrine tumour (NET) imaging. This study evaluated the impact of attenuation correction (AC) on SRS SPECT data in patients examined by SPECT-CT. METHODS: Planar scintigraphy and SPECT-CT of 17 patients (10 men, seven women; age, 40-74 years; mean, 62 years) suffering from NET were included. For the visual assessment of AC, the intensity and contrast of foci classified as pathological were rated in both the non-attenuation corrected (NAC) and the attenuation corrected (AC) SPECT images using a 5-point score. The change in signal intensity after AC was semiquantified two-fold for each focus in both SPECT(AC) and SPECT(NAC): firstly by using tumour-to-background (TB) ratios (defined as T(max)/B(mean)) for the determination of a TB(AC)/TB(NAC) ratio. Secondly, by a T(max,AC)/T(max,NAC) ratio. Both ratios were correlated to the focus depth. RESULTS: A total of 46 pathological foci were found. Focus contrast and intensity significantly increased in 14/46 foci (30%) after AC (mean, 3.7-4.0) in the visual analysis (P<0.001). While TB ratios increased only in 24/46 foci after AC and no correlation between the T(BAC)/T(BNAC) ratio and focus depth (r=0.027; P=0.856) was found, T(max) was higher after AC in all foci and the T(max,AC)/T(max,NAC) ratio showed the expected correlation to focus depth (r=0.650; P<0.01), indicating the superiority of the Tmax approach for the demonstration of the effects of attenuation correction on focal uptake. CONCLUSION: Attenuation correction of SRS SPECT data by SPECT-CT results in visually more clearly contrasted foci. Moreover, as focus intensity increases, especially in the more centrally localised foci, CT-based AC has a potential to further improve the sensitivity of SRS SPECT.     

The cell growth,morphology and immunocytochemistry of novel cell line established from a bone marrow of the patient with therapy-related myelodysplastic syndrome,entitled PC-MDS

We report on cell growth, morphology, and immunocytochemistry of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome who had no overt leukemia post-MDS phase. This cell population consisted of fast-growing mononuclear cells. Standard cytochemistry methods for detection of MPO, lipids, glycogen and ANAE gave results as follows: MPO and SBB negative while PAS and ANAE positive. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. As the first t-MDS derived cell line it could be a new tool in evaluation of complex biology of MDS and also serves as a model for diverse in-vitro research.     

Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.

PURPOSE: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma. EXPERIMENTAL DESIGN: The in vitro and ex vivo tumor uptake of [(3)H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [(18)F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [(18)F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments. RESULTS: In vitro [(3)H]FLT and [(3)H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [(3)H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [(3)H]FDG uptake was gradual and less pronounced. Tumor uptake of [(3)H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [(3)H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [(18)F]FLT and [(18)F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [(18)F]FLT uptake and histologic Ki-67 distribution in preliminary studies. CONCLUSIONS: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.     

Molecular imaging with 123I-FIAU, 18F-FUdR, 18F-FET, and 18F-FDG for monitoring herpes simplex virus type 1 thymidine kinase and ganciclovir prodrug activation gene therapy of cancer.

The ability to monitor tumor responses during prodrug activation gene therapy and other anticancer gene therapies is critical for their translation into clinical practice. Previously, we demonstrated the feasibility of noninvasive in vivo imaging with 131I-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil (131I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here we tested the efficacy of SPECT with 123I-FIAU and PET with 5-18F-fluoro-2'-deoxyuridine (18F-FUdR), 2-18F-fluoroethyl-L-tyrosine (18F-FET), and 18F-FDG for monitoring tumor responses during prodrug activation gene therapy with HSV1-tk and ganciclovir (GCV). METHODS: In the flanks of FVB/N female mice, 4 tumors per animal were established by subcutaneous injection of 1 x 10(5) cells of NG4TL4 sarcoma cells, HSV1-tk-transduced NG4TL4-STK cells, or a mixture of these cells in different proportions to model different efficacies of transfection and HSV1-tk gene expression levels in tumors. Ten days later, the animals were treated with GCV (10 mg/kg/d intraperitoneally) for 7 d. Gamma-Imaging with 123I-FIAU and PET with 18F-FUdR, 18F-FET, and 18F-FDG were performed before and after initiation of therapy with GCV in the same animal. RESULTS: Before GCV treatment, no significant difference in weight and size was found in tumors that expressed different HSV1-tk levels, suggesting similar in vivo proliferation rates for NG4TL4 and NG4TL4-STK sarcomas. The accumulation of 123I-FIAU at 24 h after injection was directly proportional to the percentage of NG4TL4-STK cells in the tumors. The 123I-FIAU accumulation at 4 and 7 d of GCV therapy decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. Tumor uptake of 18F-FUdR in all HSV1-tk-expressing tumors also decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. The accumulation of 18F-FET decreased minimally (about 1.5-fold) and 18F-FDG decreased only 2-fold after 7 d of GCV therapy, and the degree of reduction was proportional to the percentage of HSV1-tk-positive tumor cells. CONCLUSION: We have shown that gamma-camera imaging with 123I-FIAU was the most reliable method for prediction of tumor response to GCV therapy, which was proportional to the magnitude of HSV1-tk expression in tumor tissue. 123I-FIAU imaging can be used to verify the efficacy of elimination of HSV1-tk-expressing cells by therapy with GCV. PET with 18F-FUdR reliably visualizes proliferating tumor tissue and is most suitable for the assessment of responses in tumors undergoing HSV1-tk plus GCV prodrug activation gene therapy. PET with 18F-FDG or 18F-FET can be used as additional "surrogate" biomarkers of the treatment response, although these radiotracers are less sensitive than 18F-FUdR for monitoring tumor responses to prodrug activation gene therapy with HSV1-tk and GCV in this sarcoma model.     

Iron overload in congenital haemolytic anaemias: role of hepcidin and cytokines and predictive value of ferritin and transferrin saturation

Iron overload (IO) is poorly investigated in the congenital haemolytic anaemias (CHAs), a heterogeneous group of rare inherited diseases encompassing abnormalities of the erythrocyte membrane and metabolism, and defects of the erythropoiesis. In this study we systematically evaluated routine iron parameters and cardiac and hepatic magnetic resonance imaging, together with erythropoietin, hepcidin, non-transferrin bound iron (NTBI), and cytokine serum levels in patients with different CHAs. We found that 40% of patients had a liver iron concentration (LIC) >4 mg Fe/g dry weight. Hepatic IO was associated with ferritin levels (P = 0·0025), transferrin saturation (TfSat, P = 0·002) and NTBI (P = 0·003). Moreover, ferritin >500 μg/l plus TfSat >60% was demonstrated as the best combination able to identify increased LIC, and TfSat alteration as more important in cases with discordant values. Possible confounding factors, such as transfusions, hepatic disease, metabolic syndrome and hereditary haemochromatosis-associated mutations, had negligible effects on IO. Erythropoietin and hepcidin levels were increased in CHAs compared with controls, correlating with LIC and ferritin, respectively. Regarding cytokines, γ-interferon (IFN-γ) was increased, and both interleukin 6 and IFN-γ levels positively correlated with ferritin and hepcidin levels. Overall, these findings suggest the existence of a vicious cycle between chronic haemolysis, inflammatory response and IO in CHAs.     

Factors affecting recurrence after incisional hernia repair

Incisional hernias occur primarily as a result of high tension and inadequate healing of a previous incision, the latter of which is frequently related to infection at the surgical site. Despite recent advances in operative techniques, the recurrence rate remains unacceptably high. To evaluate the impact of different predisposing factors for the recurrence of incisional hernia, we reviewed retrospectively the medical records of 297 patients who had undergone incisional herniorrhaphy (188 tissue repairs, 109 mesh repairs) in our hospital. Demographic data (age and gender), type of repair, body mass index, hernia size, presence of chronic illnesses and wound complications were evaluated in a univariate and multivariate manner analysis. The overall recurrence rate was 30.3%, with the recurrence rate in patients who underwent tissue repair being 39.4% and that in patients following prosthetic repair 14.6%. The recurrence rate was significantly influenced by type of repair, obesity, hernia size, wound healing disorders and some chronic comorbidities. We conclude that it is necessary to become familar with the risk factors for recurrence of incisional hernia in order to eliminate or decrease their effect on the positive outcome of incisional herniorrhaphy.