Aydin Sav

Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of spinal cord and cortical motoneurons. Despite improved understanding of the mechanisms underlying ALS, in clinical practice the management of ALS remains essentially supportive and focused on symptom relief. However, over the past few years stem cell research has expanded greatly as a tool for developing potential new therapies for treating incurable neurodegenerative diseases. METHODS Thirteen patients with sporadic amyotrophic lateral sclerosis (SALS) were included in this study, and bone marrow (BM)-derived hematopoietic progenitor stem cells were used. We selected patients with bulbar involvement and severe loss of movement. Our aim was to put the stem cells into the end of the brain stem and at the beginning of the spinal cord because the blood-brain barrier is intact in ALS and this region was the most affected part in our patients. Under general anesthesia, a total laminectomy was performed at the C1-C2 level. Stem cells were injected to the anterior part of the spinal cord. RESULTS During the follow-up of 1 year after stem cell implantation, nine patients became much better compared with their pre-operative status, confirmed by electro neuro myography (ENMG). One patient was stable without any decline or improvement in his status. Three patients died 1.5, 2 and 9 months, respectively, after stem cell therapy as a result of lung infection and myocardial infarction (MI). DISCUSSION These results show that stem cell therapy is a safe, effective and promising treatment for ALS patients.

Serum leptin levels, skin leptin and leptin receptor expression in psoriasis

Background  Recent studies support the relation of psoriasis with obesity and cardiovascular disease. Leptin, a peptide hormone secreted predominantly from adipose tissue, is involved in the regulation of energy intake and expenditure. Recently, it has been shown to have several immunological effects including induction of proinflammatory cytokine production.

Effects of pulsed versus conventional radiofrequency current on rabbit dorsal root ganglion morphology

Lesioning using radiofrequency (RF) current has been increasingly used in clinical practice for the treatment of pain syndromes. Although formation of heat causing “thermocoagulation” of the nervous tissues is thought to be responsible of the clinical outcome, a more recent modality of RF application named pulsed radiofrequency (PRF) delivers the RF current without producing destructive levels of heat. In our study, we compared the effects of conventional RF (CRF) and PRF on rabbit dorsal root ganglion (DRG) morphology, including also control and sham operated groups. The setting of the experiment and the RF parameters used were similar to those used in current clinical practice. The specimens were analyzed both with light microscopy and electron microscopy, two weeks after the procedure. At the light microscopic level, all groups had preserved the normal DRG morphology and no differences were observed between them. In the electron microscopic analysis there were no pathological findings in the control and sham operated groups. But the ganglion cells in the RF groups had enlarged endoplasmic reticulum cisterns and increased number of cytoplasmic vacuoles which were more evident in the CRF group. Some of the ganglion cells in the CRF group had mitochondrial degeneration, nuclear membrane disorders or loss of nuclear membrane and neurolemma integrity. The myelinated and unmyelinated nerve fibers were of normal morphology in all groups. Our results suggest that PRF application is less destructive of cellular morphology than CRF at clinically used “doses”. Before making certain judgements, more experimental and clinical studies should be planned.

The effects of the size of liposuction cannula on adipocyte survival and the optimum temperature for fat graft storage: an experimental study

BACKGROUND Determining the most advantageous size of liposuction cannula and injection needles in terms of adipocyte viability could help to increase fat graft survival. When recurrent injections are necessary, storing fat tissue which is harvested during the first operation could be a practical solution if it is stored at an appropriate temperature providing the highest amount of viable fat cells. METHODS Fat tissue was removed from the abdomen of 10 consecutive female patients by 6-, 4- and 2-mm-diameter liposuction cannulas. Fat tissue harvested with the 6mm cannula was injected through 14, 16 and 20 g needles and collected in separate tubes. An additional three tubes of fat samples were prepared from fat tissue obtained with the 6mm cannula to be stored at +4, -20 and -80 degrees C for 2 weeks. Viability of the fat grafts was evaluated by fat cell isolation with collagenase digestion and staining with supravital dye and counting adipocytes with a haemocytometer. RESULTS The viability of fat grafts harvested with the 6mm cannula was higher than grafts obtained with smaller cannulas. The viability of fat grafts injected through 14, 16 and 20 g needles were similar to each other. The viability of fat grafts stored at +4 degrees C was similar to fresh tissue whereas freezing fat grafts caused significant loss of viable adipocytes compared to fresh tissue. CONCLUSIONS The use of larger liposuction cannulas for fat tissue harvesting provides more viable fat grafts. A temperature of +4 degrees C could be proposed as an effective and easily available way of storing fat grafts for at least 2 weeks.

Detection of KIAA1549-BRAF fusion transcripts in formalin-fixed paraffin-embedded pediatric low-grade gliomas.

Alterations of BRAF are the most common known genetic aberrations in pediatric gliomas. They frequently are found in pilocytic astrocytomas, where genomic duplications involving BRAF and the poorly characterized gene KIAA1549 create fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point mutations are less common and generally occur in nonpilocytic tumors. The development of BRAF inhibitors as drugs has created an urgent need for robust clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion transcripts have been detected in frozen tissue, however, methods for FFPE tissue have not been reported. We developed a panel of FFPE-compatible quantitative RT-PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of these assays to a collection of 51 low-grade pediatric gliomas showed 97% sensitivity and 91% specificity compared with fluorescence in situ hybridization or array comparative genomic hybridization. In parallel, we assayed samples for the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further support previous observations that these two alterations of the BRAF, KIAA1549 fusions and V600E point mutations, are associated primarily with pilocytic astrocytomas and nonpilocytic gliomas, respectively. These results show that fusion transcripts and mutations can be detected reliably in standard FFPE specimens and may be useful for incorporation into future studies of pediatric gliomas in basic science or clinical trials.

Tenascin in meningioma: Expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape

OBJECTIVE : Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Methods: Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transciptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. Results: The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression byt not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two speciemens. Conclusion: In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

Expression of growth factors and structural proteins in chordomas: basic fibroblast growth factor, transforming growth factor alpha, and fibronectin are correlated with recurrence.

OBJECTIVE To test the hypothesis that the expression of certain growth factors and/or structural proteins is correlated with the biological behavior of cranial base chordomas. METHODS The study investigated 14 pathological specimens of cranial base chordomas from patients who were monitored for at least 2 years after their initial operations. Some cases involved multiple tumor recurrences and multiple operations. For those patients, the time to recurrence after each operation was recorded and a mean value was calculated. Nine patients with mean times to recurrence of 24 months or more or with 24 months of follow-up monitoring without recurrence after single operations were designated the “good-prognosis” group. Five patients with mean times to recurrence of less than 24 months were designated the “poor-prognosis” group. In each case, only the specimen from the initial operation was studied. Multiple sequential sections were cut from paraffin-embedded blocks of tissue and immunohistochemically prepared for detection of three growth factors and three structural proteins, i.e., basic fibroblast growth factor, transforming growth factor &agr;, vascular endothelial growth factor, fibronectin, collagen III, and collagen IV. Intensity of expression was graded by using a four-tier system (Grades 0, 1, 2, and 3). Levels of expression of the molecules in the two groups were evaluated and compared. RESULTS The mean transforming growth factor &agr; expression intensity grades for the good- and poor-prognosis groups were 0.8 and 2.6, respectively, and the corresponding mean basic fibroblast growth factor grades were 1.4 and 2.6. For both groups, the mean grade for vascular endothelial growth factor expression was 0.6. For fibronectin, the mean staining grades for the good- and poor-prognosis groups were 2.2 and 3.0, respectively. The corresponding mean intensities for collagen III were 1.1 and 0.8, and those for collagen IV were 2.5 and 2.6. CONCLUSION Our descriptive data from immunohistochemical analyses of chordomas suggest that high levels of transforming growth factor &agr; and basic fibroblast growth factor expression are linked to higher rates of recurrence. Strong fibronectin expression may also be a marker of aggressive biological behavior.

Spinal solitary fibrous tumor: seventh reported case and review of the literature

We present the clinical, radiological, and pathological features of a solitary fibrous tumor in the spinal cord. This case is the seventh spinal solitary fibrous tumor in the literature. The tumor caused clinical symptoms in a 70-year-old female, which indicated compression of the spinal cord. Magnetic resonance imaging showed an intradural extramedullary mass at T3 vertebral level. Surgically, the tumor was firm, in an intradural extramedullary location and attached to the dura. Histologically, the tumor was composed of spindle cells in a collagen-rich matrix but exhibited regional variations. CD34 and vimentin were diffusely positive during immunohistochemical stain testing. The tumor displayed no positive staining for epithelial membrane antigen, cytokeratin, S-100 protein, smooth muscle actin or desmin. The Ki-67 labeling index was low. Solitary fibrous tumors have been found in a variety of locations suggesting that a solitary fibrous tumor has a mesenchymal origin. This rare tumor should be considered in the differential diagnosis of spinal tumors.Spinal Cord (2001) 39, 57–60.

Anaplastic Pleomorphic Xanthoastrocytomas

Malignancy potential of pleomorphic xanthoastrocytomas (PXAs) has rather been an underestimated reality. We report the case of a 13-year-old boy who presented with signs of increased intracranial pressure. The child had been epileptic since the age of 2. Computed tomography and magnetic resonance scans revealed a huge left frontal mass. At surgery, a subtotal excision was accomplished. Histopathological diagnosis was anaplastic PXA (grade III; WHO, 2000). The tumor showed an increased mitotic index and minimal endothelial proliferation. The patient died 3.5 months later due to a fatal intracranial hemorrhage. A review of the entire PXA literature revealed 15 well-documented cases of PXA with subsequent malignant transformation and 11 cases of primary anaplastic PXA. The prognosis was grim for both subsets of patients. Anaplastic PXAs clearly represent the transition between the original PXA concept and lipidized giant-cell glioblastoma.

Intraoperative magnetic resonance spectroscopy for identification of residual tumor during low-grade glioma surgery: Clinical article

OBJECT The authors had previously shown that 3-T intraoperative MRI (ioMRI) detects residual tumor tissue during low-grade glioma and that it helps to increase the extent of resection. In a proportion of their cases, however, the ioMRI disclosed T2-hyperintense areas at the tumor resection border after the initial resection attempt and prompted a differential diagnosis between residual tumor and nontumoral changes. To guide this differential diagnosis the authors used intraoperative long-TE single-voxel proton MR spectroscopy (ioMRS) and tested the correlation of these findings with findings from pathological examination of resected tissue. METHODS Patients who were undergoing surgery for hemispheric or insular WHO Grade II gliomas and were found to have T2 changes around the resection cavity at the initial ioMRI were prospectively examined with ioMRS and biopsies were taken from corresponding localizations. In 14 consecutive patients, the ioMRS diagnosis in 20 voxels of interest was tested against the histopathological diagnosis. Intraoperative diffusion-weighted imaging (ioDWI) was also performed, as a part of the routine imaging, to rule out surgically induced changes, which could also appear as T2 hyperintensity. RESULTS Presence of tumor was documented in 14 (70%) of the 20 T2-hyperintense areas by histopathological examination. The sensitivity of ioMRS for identifying residual tumor was 85.7%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 75%. The specificity of ioDWI for surgically induced changes was high (100%), but the sensitivity was only 60%. CONCLUSIONS This is the first clinical series to indicate that ioMRS can be used to differentiate residual tumor from nontumoral changes around the resection cavity, with high sensitivity and specificity.