Buckwheat conservation as hay or silage: agronomic evaluation, nutritive value, conservation quality, and intake by lactating dairy goats.

Buckwheat was conserved either as silage at two dry matter (DM) levels attained with (wilted silage (WS), 313 g/kg) and without wilting (direct cut silage (DS), 171 g/kg) or as hay (856 g/kg) and was included in the isonitrogenous and isocaloric total mixed ration (TMR) of four groups of six Saanen goats each at the rate of 200 g/kg DM. Ensiling buckwheat at low DM led to a poorly fermented silage with higher ammonia-N and butyric acid contents and extensive growth of enterobacteria and mold-yeast than WS. The DM recovery of DS was lower than that of WS. The total phenol (TP) content of buckwheat was also preserved more efficiently in hay than in DS. The nutritive value of hay was higher than that of the silages because hay had less fiber contents but more non-fiber carbohydrates and total digestible nutrients. The decrease in nutritive value in buckwheat silages, in particular for DS, increased the nutrient intensity in the concentrated feed. The DM intake of goats fed DS TMR tended to be lower (P=0.09) than that of the goats fed WS TMR in the first week of the experiment, but the goats quickly adapted to the poorly fermented silage and did not reduce their overall DM intake. The DS, WS, and hay TMRs did not affect fat corrected milk yield but increased the milk TPs compared to a TMR with legume-grass hay. It was concluded that buckwheat hay and silages are well accepted by dairy goats, but the DM content of buckwheat at ensiling may require over 330 g/kg for producing well-fermented silages.

Ankaferd blood stopper enhances healing after osseous grafting in patients with intrabony periodontal defects.

BACKGROUND AND OBJECTIVE: The aim of this clinical study were to compare the clinical efficacy of ankaferd blood stopper (ABS) when used in combination with autogenous cortical bone graft (ACB) in the treatment of intrabony periodontal defects. MATERIAL AND METHODS: The study was planned as a split-mouth design. Fifteen patients with chronic periodontitis at 30 sites (six men, nine women; 42 ± 7 years) were included. Treatment sites had probing pocket depths (PPD) of ≥ 6 mm and osseous defect depths of ≥ 4 mm as radiographically assessed. Following the initial periodontal therapy, patients were randomly assigned to two treatments in contralateral areas of the dentition: ACB + ABS or ACB alone. At baseline and 6 mo after surgery, clinical parameters of plaque index, gingival index, PPD, clinical attachment level and gingival recession (GR) were recorded. The primary outcome variable was the change in clinical attachment level between baseline and 24 wk after surgery. Gingival crevicular fluid samples were collected immediately before surgery and at 2, 4, 6, 12 and 24 wk after the surgery. Gingival crevicular fluid volume was calculated and vascular endothelial growth factor levels in gingival crevicular fluid were measured. RESULTS: PPD decreased, clinical attachment level improved and gingival index decreased significantly in response to both modes of treatment (p < 0.05). Both treatment modalities resulted in a significant gain in radiographic bone levels compared to baseline (p < 0.05). Intergroup comparisons showed that there was a significantly higher gain in clinical attachment level in the ABS/ACB group compared to ACB group (p < 0.05) with significantly less GR (p < 0.05). Similarly, vascular endothelial growth factor concentration in gingival crevicular fluid was significantly higher in the ABS/ACB group at postoperative weeks 2 and 4 compared to the ACB group (p < 0.01). CONCLUSIONS: The findings suggest that ABS enhances the soft tissue healing during the periodontal defect fill by the ACB by stimulating angiogenesis and vascular endothelial cell function, prevents GR and thereby increases the clinical attachment gain.

Evaluation of gingival alterations in rats medicated with cyclosporine A, tacrolimus and sirolimus: a stereological study.

BACKGROUND AND OBJECTIVE: It has previously been shown that both cyclosporine A and tacrolimus cause gingival overgrowth in the rat. We proposed that sirolimus may play an important role in decreasing the severity of gingival overgrowth. Therefore, the aim of this study was to evaluate the gingival changes induced by immunosuppressants, in the presence and absence of sirolimus, using histopathology and stereological methods. MATERIAL AND METHODS: Thirty-six male Sprague-Dawley rats were distributed into six treatment groups, each containing six rats, as follows: (i) cyclosporine A for 8 wk; (ii) tacrolimus for 8 wk; (iii) sirolimus for 8 wk; (iv) cyclosporine A + sirolimus for 8 wk; (v) tacrolimus + sirolimus for 8 wk; and (vi) distilled water for 8 wk. Histomorphometric analyses included measurements of epithelial thickness and connective tissue width and height. Stereological analyses included measurements of volumetric densities of fibroblasts (Vf ), collagen fibers (Vcf ) and blood vessels (Vbv ). RESULTS: Connective tissue width and height were significantly increased in cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05), and epithelial thickness was significantly increased in the cyclosporine A group and tacrolimus group compared with the control group (p < 0.05). Vf was significantly increased in the cyclosporine A group and the tacrolimus group compared with the control group (p < 0.05), whereas Vcf and Vbv were significantly increased in the cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05). CONCLUSION: The results of the study suggest that sirolimus seems not to be associated with gingival overgrowth, and combined usage of sirolimus and immunosuppressants decreases the severity of gingival overgrowth.

Assessment of periostin levels in serum and gingival crevicular fluid of patients with periodontal disease.

BACKGROUND AND OBJECTIVE: Periostin, a secreted adhesion molecule essential for periodontal tissue integrity, is highly expressed in the periodontal ligament and plays a critical role in tooth and bone development. The purpose of this study was to investigate periostin levels in the gingival crevicular fluid and serum of patients with periodontal disease and compare them with those of healthy individuals. MATERIAL AND METHODS: Eighty individuals (41 males and 39 females; age range: 25-48 years) were enrolled in the study. Individuals were divided into three groups following clinical and radiographic examinations: the periodontal-healthy group (n = 20), gingivitis group (n = 30) and chronic periodontitis group (n = 30). Gingival crevicular fluid and serum samples were collected and periostin levels were determined using the enzyme-linked immunosorbent assay. RESULTS: The total amount and concentration of periostin decreased in gingival crevicular fluid with the progression and severity of the disease from healthy controls to gingivitis and to chronic periodontitis groups and differed significantly (p < 0.05). However, there was no significant difference in serum periostin concentration within all groups (p > 0.05). Periostin in gingival crevicular fluid negatively correlated with the gingival index in the periodontal disease groups, whereas it is inversely correlated with the clinical attachment level only in the periodontitis group (p < 0.05). When all the clinical groups were examined together, the periostin concentration negatively correlated with clinical attachment level and gingival index; moreover, total periostin positively correlated with periostin concentration and clinical attachment level (p < 0.05). CONCLUSIONS: The periostin levels in gingival crevicular fluid decreased proportionally with the progression and severity of periodontal disease, and negatively correlated with the clinical parameters. Within the limits of the study, the periostin level in gingival crevicular fluid can be considered a reliable marker in the evaluation of periodontal disease susceptibility and activity.

The role of phosphatase and tensin homolog in drug-induced gingival overgrowth.

BACKGROUND AND OBJECTIVE: We proposed that phosphatase and tensin homolog (PTEN) might be one of the signaling proteins that alter the balance between cell growth and cell death in drug-induced gingival overgrowth. The aim of this study was to investigate the expression of PTEN in subjects using cyclosporine A and to analyze the relationship between PTEN and cell proliferation marker, proliferating cell nuclear antigen (PCNA), in cyclosporine A-induced gingival overgrowth. MATERIAL AND METHODS: In total, samples from 36 subjects, i.e. 24 cyclosporine A-mediated renal transplant patients with gingival overgrowth (n = 12) or without gingival overgrowth (n = 12) and 12 matched periodontally healthy subjects, were included in the study. PTEN and PCNA expressions in gingival tissues were analyzed using immunohistochemistry, PTEN expression was also analyzed by western blot. PTEN immunoreactivity was calculated with a histologic score (HSCORE) value and PCNA immunoreactivity was calculated with the PCNA-proliferative index. RESULTS: Phosphatase and tensin homolog HSCORE for the group with gingival overgrowth was found to be significantly lowest compared to the group without gingival overgrowth and the control group (p < 0.001) while the highest PTEN HSCORE was found in the control group. In addition, the PTEN HSCORE for the group without gingival overgrowth was significantly lower compared to controls (p < 0.001). The highest PCNA-proliferative index score was observed in the group with gingival overgrowth while the lowest score was observed in the control group (p < 0.001). The immunoblot signal for PTEN was significantly decreased in the group with gingival overgrowth compared to the group without gingival overgrowth and the control group (p < 0.001). Western blot results were different from immunohistochemistry and revealed there was no significant difference between the without gingival overgrowth and the control group (p > 0.05). CONCLUSION: Our results showing decreased PTEN levels in patients with gingival overgrowth supported with increased PCNA expression suggested that PTEN might take part in the imbalance between cell proliferation and death in drug-induced gingival overgrowth.

FFPE++: Improving the quality of formalin-fixed paraffin-embedded tissue imaging via contrastive unpaired image-to-image translation.

Formalin-fixation and paraffin-embedding (FFPE) is a technique for preparing and preserving tissue specimens that has been utilized in histopathology since the late 19th century. This process is further complicated by FFPE preparation steps such as fixation, processing, embedding, microtomy, staining, and coverslipping, which often results in artifacts due to the complex histological and cytological characteristics of a tissue specimen. The term "artifacts" includes, but is not limited to, staining inconsistencies, tissue folds, chattering, pen marks, blurring, air bubbles, and contamination. The presence of artifacts may interfere with pathological diagnosis in disease detection, subtyping, grading, and choice of therapy. In this study, we propose FFPE++, an unpaired image-to-image translation method based on contrastive learning with a mixed channel-spatial attention module and self-regularization loss that drastically corrects the aforementioned artifacts in FFPE tissue sections. Turing tests were performed by 10 board-certified pathologists with more than 10 years of experience. These tests which were performed for ovarian carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, and papillary thyroid carcinoma, demonstrate the clear superiority of the proposed method in many clinical aspects compared with standard FFPE images. Based on the qualitative experiments and feedback from the Turing tests, we believe that FFPE++ can contribute to substantial diagnostic and prognostic accuracy in clinical pathology in the future and can also improve the performance of AI tools in digital pathology. The code and dataset are publicly available at https://github.com/DeepMIALab/FFPEPlus.

A robust image segmentation and synthesis pipeline for histopathology.

Significant diagnostic variability between and within observers persists in pathology, despite the fact that digital slide images provide the ability to measure and quantify features much more precisely compared to conventional methods. Automated and accurate segmentation of cancerous cell and tissue regions can streamline the diagnostic process, providing insights into the cancer progression, and helping experts decide on the most effective treatment. Here, we evaluate the performance of the proposed PathoSeg model, with an architecture comprising of a modified HRNet encoder and a UNet++ decoder integrated with a CBAM block to utilize attention mechanism for an improved segmentation capability. We demonstrate that PathoSeg outperforms the current state-of-the-art (SOTA) networks in both quantitative and qualitative assessment of instance and semantic segmentation. Notably, we leverage the use of synthetic data generated by PathopixGAN, which effectively addresses the data imbalance problem commonly encountered in histopathology datasets, further improving the performance of PathoSeg. It utilizes spatially adaptive normalization within a generative and discriminative mechanism to synthesize diverse histopathological environments dictated through semantic information passed through pixel-level annotated Ground Truth semantic masks.Besides, we contribute to the research community by providing an in-house dataset that includes semantically segmented masks for breast carcinoma tubules (BCT), micro/macrovesicular steatosis of the liver (MSL), and prostate carcinoma glands (PCG). In the first part of the dataset, we have a total of 14 whole slide images from 13 patients' liver, with fat cell segmented masks, totaling 951 masks of size 512 × 512 pixels. In the second part, it includes 17 whole slide images from 13 patients with prostate carcinoma gland segmentation masks, amounting to 30,000 masks of size 512 × 512 pixels. In the third part, the dataset contains 51 whole slides from 36 patients, with breast carcinoma tubule masks totaling 30,000 masks of size 512 × 512 pixels. To ensure transparency and encourage further research, we will make this dataset publicly available for non-commercial and academic purposes. To facilitate reproducibility and encourage further research, we will also make our code and pre-trained models publicly available at https://github.com/DeepMIALab/PathoSeg.

Activity of platelet activating factor acetylhydrolase following phase I periodontal therapy.

OBJECTIVE: Elevated levels of platelet activating factor (PAF), a potent inflammatory mediator in periodontal disease and decreased PAF levels following periodontal surgical therapy have been previously detected in gingival tissues and gingival crevicular fluid (GCF). Platelet activating factor acetylhydrolase (PAF-AH) is a calcium-independent phospholipase A2 that catalyses the hydrolysis of PAF, thereby inactivating this mediator The hypothesis, a relationship between activity of PAF-AH and healing following periodontal therapy, was tested by detecting activity of PAF-AH in GCF samples collected from sites that had undergone phase I periodontal therapy with generalized chronic periodontitis. METHODS: Twenty patients with generalized chronic periodontitis were divided into two groups (n = 10): group 1 with probing pocket depth (PPD) 4-5 mm and group 2 with PPD > or = 6-8 mm. Clinical parameters were recorded and GCF was sampled before phase I periodontal therapy and at the 2nd, 7th, 14th, 21st and 28th day follow-up evaluation visits. Activity of PAF-AH in GCF was analysed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Probing pocket depth at the 21st and 28th day in group 1, and PPD at the 14th, 21st and 28th day in group 2 were significantly decreased when compared to the baseline values (p < 0.001). Activity of PAF-AH (micromol/ml) was significantly decreased at the 7th, 14th, 21st and 28th day following phase I periodontal therapy in both groups 1 and 2 compared to the baseline values (p < 0.05). CONCLUSION: Platelet activating factor acetylhydrolase is detectable in GCF by ELISA and showed a continuous decrease following phase I periodontal therapy. Changes in the PAF-AH activity would be a progressive marker of periodontal healing to evaluate the success of periodontal therapies.

TNF-α, IL-1ß, and oxidative stress during fracture healing with or without ankaferd.

AIMS: Whether ankaferd blood stopper (ABS) has a negative or positive effect on bone union during fracture healing is unknown. The purpose of this study was to evaluate the serum changes of oxidative stress markers, Tumor Necrosis Factor-α (TNF-α), Interleukin-1ß (IL-1ß), and Interleukin-10 (IL-10) during fracture healing process with or without ABS application to bone fracture. MATERIAL AND METHODS: Eight rats were used as a control group (1) that was not subject to fracture. The remaining 48 rats were divided into six groups, 8 rats in each. The femoral shaft fracture was produced by cutting with bone-scissors. One ml of ABS was applied on the fracture region in groups 3 (7th day), 5 (21st day), and 7 (45th day) or saline instead of ABS on the fracture regions in groups 2 (7th day), 4 (21st day), and 6 (45th day). Radiographs and above parameters were examined on post-fracture days 7, 21, and 45. RESULTS: Malondialdehyde and protein carbonyls were measured in high levels in the groups 2 and 4 with respect to control. Their levels did not change statistically in the experimental groups after ABS application. The values of TNF-α and IL-1ß were elevated on 7th post-fracture day according to control, but were lower (by 11.86 % and 44.48 %) in the group 3 treated with ABS comparing to group 2. Radiographic examination indicated a low callus formation on fracture union in the femoral fractures of groups 3 and 5 treated with ABS. CONCLUSION: The present findings may suggest that ABS application seems to be ineffective on fracture union in early fracture healing period, except for bleeding control (Tab. 2, Fig. 3, Ref. 26).

Seizure characteristics and control following resection in 332 patients with low-grade gliomas.

OBJECT: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS: The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS: Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). CONCLUSIONS: The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.

Clinical aspects and risk factors of nosocomial Stenotrophomonas maltophilia bacteremia episodes in a Turkish intensive care unit.

Stenotrophomonas maltophilia is an important nosocomial pathogen with increasing frequency in recent years, especially in immunocompromised and clinically debilitated patients. The aim of this study is to describe the characteristics of 35 episodes of S. maltophilia bacteremia at Celal Bayar University hospital in Turkey over a 3-year period from January 2003 to December 2005. Cases were identified with microbiology laboratory records and clinical data were collected from the medical record of each patient. The source of bacteremia was central venous catheter (CVC) in 65.7% (23) and respiratory tract infection in 2.9% (1) of episodes while the source of bacteremia was unknown in 11 (31.4%) episodes of bacteremia. Factors significantly associated with mortality were age of > or =65 years, APACHE score of > or =16, the presence of the total parenteral nutrition, anemia, low creatinine clearance level and shock. The most sensitive antibiotic was found as trimethoprim-sulfamethoxazole (91.4%) in antibiotic susceptibility testing of the isolates. Susceptibilities of piperacillin-tazobactam and netilmicin which frequently used antibiotics as an empirical therapy were 62.8% and 68.6%, respectively.

Biomass yield and feeding value of rye, triticale, and wheat straw produced under a dual-purpose management system.

Dual-purpose management of winter cereals for grazing and grain production provides highly nutritive forage for ruminants in the spring and may positively affect straw feeding value. A 2-yr study investigated the effect of spring defoliation of triticale, wheat, and rye at the tillering and stem elongation stages on total biomass, grain yields, and straw quality. Furthermore, straws of spring-defoliated and undefoliated (control) cereal crops were evaluated for nutritional value and voluntary intake as a means of assessing the efficiency of dual-purpose management systems from the winter feeding context as well. The feeding study consisted of 9 total mixed rations (TMR), each containing 35% triticale, rye, or wheat straw obtained under 3 spring-defoliation regimens. The TMR were individually fed to fifty-four 1-yr-old Anatolian Merino ewes for 28 d. Defoliation of the crops at tillering did not affect the total biomass production or grain yields. However, biomass and grain yields were reduced ( < 0.01) by 55 and 52%, respectively, in crops defoliated at stem elongation. Straw of spring-defoliated cereals had less NDF and ADF concentrations ( < 0.01) but greater CP ( < 0.01), nonfiber carbohydrates ( < 0.01), and ME concentrations ( < 0.01) compared with straw from undefoliated crops. The increase in the nutritive value of straw led to greater nutrient digestion ( < 0.01) and intake of DM and OM of ewes ( < 0.01). However, sheep live weight gain did not differ among treatments ( > 0.77). This study indicated that straw feeding value and digestibility can be increased through spring defoliation.

Volumetric extent of resection and residual contrast enhancement on initial surgery as predictors of outcome in adult patients with hemispheric anaplastic astrocytoma.

OBJECT: To investigate the prognostic significance of the volumetrically assessed extent of resection on time to tumor progression (TTP), overall survival (OS), and tumor recurrence patterns, the authors retrospectively analyzed preoperative and postoperative tumor volumes in 102 adult patients from the time of the initial resection of a hemispheric anaplastic astrocytoma (AA). METHODS: The quantification of tumor volumes was based on a previously described method involving computerized analysis of magnetic resonance (MR) images. Analysis of contrast-enhancing tumor volumes on T1-weighted MR images was conducted for 67 patients who had contrast-enhancing tumors. Measurements of T2 hyperintensity were obtained for all 102 patients in the study. The presence or absence of preresection enhancement, actual volume of this enhancement, and the percentage of preoperative enhancement as it relates to the total T2 tumor volume did not have a statistically significant relationship to TTP or OS. In addition to age, the volume of residual disease measured on T2-weighted MR images was the most significant predictor of TTP (p < 0.001), and residual contrast-enhancing tumor volume was the most significant predictor of OS (p = 0.003) on multivariate analysis. In contrast to low-grade gliomas, there was no statistically significant relationship between the extent of resection and histological characteristics at the time of recurrence, that is, tumor Grade III compared with Grade IV. CONCLUSIONS: Data from this retrospective analysis of a histologically uniform group of hemispheric AAs treated in the MR imaging era suggest that residual tumor volumes, as documented on postoperative imaging studies, may be a prognostic factor for TTP and OS for this patient population.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial.

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

New missions for an old agent: granulocyte-colony stimulating factor in the treatment of stroke patients.

Granulocyte-colony stimulating factor (G-CSF) has a multimodal neuroprotective profile and the cumulative preclinical data from numerous translational studies statistically confirmed the efficacy of G-CSF as a treatment option in ischemic stroke. G-CSF activates anti-apoptotic, antioxidative, and anti-inflammatory signaling pathways and stimulates angiogenesis and neurogenesis. In this review, we summarize the role of G-CSF and the corresponding signal transduction pathways regulated by G-CSF in neuroprotection and discuss its potential as a new drug for stroke treatment.

Advances in neurosurgical technique in the current management of brain tumors.

Despite significant advances in anatomical and functional neuroimaging modalities (eg, magnetic resonance [MR] imaging [MRI], MR spectroscopy [MRS], diffusion and perfusion MR, functional MRI [fMRI], magnetic-source imaging [MSI], diffusion tensor imaging [DTI]) and neuronavigation techniques, intraoperatively obtained functional information remains of crucial importance to the neurosurgeon, especially when operating on tumors that are located in or adjacent to functional cortical sites and subcortical pathways. This article focuses on recent advances in the surgical management of of intracerebral tumors with special emphasis on intraoperative cortical and subcortical stimulation mapping methods, and the prognostic significance of surgery on patient outcome.

Coregistration accuracy and detection of brain shift using intraoperative sononavigation during resection of hemispheric tumors.

OBJECTIVE: Sononavigation, which combines real-time anatomic ultrasound data with neuronavigation techniques, is a potentially valuable adjunct during the surgical excision of brain tumors. METHODS: In this study, we report our preliminary observations using this technology on 58 adult patients harboring hemispheric tumors. Data regarding coregistration accuracy was collected from various landmarks that typically do not shift as well as from tumor boundaries and the cortical surface. In a subset of patients, we evaluated the extent and direction of postresection brain displacement and its relationship with patient age, tumor histology, tumor volume, and use of mannitol. RESULTS: For all structures excluding the cortex, average coregistration accuracy measurements between ultrasound and preoperatively acquired magnetic resonance imaging scans were within the range of 2 mm. The most accurate alignments were obtained with the choroid plexus and the falx, and the least reliable structure in terms of coregistration accuracy was the cortical surface. CONCLUSION: Sononavigation provides real-time information during tumor removal in alignment with the preoperative magnetic resonance imaging scans, thus enabling the surgeon to detect intraoperative hemorrhage, cyst drainage, and tumor resection, and it allows for calculation of brain shift during the use of standard navigation techniques.

Nerve growth factor receptor expression in medulloblastomas and the potential role of nerve growth factor as a differentiating agent in medulloblastoma cell lines.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and nonneoplastic cell lines. In this study, our aim was to determine NGF receptor (NGFr) status in medulloblastoma specimens and cell lines and to investigate whether NGF could act as a potential differentiating agent for this common pediatric brain tumor. Paraffin-embedded tumor tissue from 10 patients with the diagnosis of medulloblastoma was retrospectively analyzed to determine the frequency of NGFr expression. Of the 10 tumor specimens evaluated, 4 were positive for NGFr; however, NGFr staining was confined to only 5 to 8% of the cells in a randomly scattered pattern. No colocalization was present with neuronal, glial, or vascular structures. In addition, two medulloblastoma cell lines established in our laboratory were also evaluated for NGFr. In this study, we also examined the effects of retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate, and NGF on medulloblastoma cell lines to evaluate their effect on morphological differentiation and NGFr expression. Although these agents failed to cause NGFr expression in our cell lines, morphological alteration was noticed in only one of the cell lines with retinoic acid. Therefore, because of the lack of de novo or induced NGFr expression, it is unlikely that NGF will be useful as a potential therapeutic differentiating agent for medulloblastomas.

Expression of glial fibrillary acidic protein in human medulloblastoma cells treated with recombinant glia maturation factor-beta.

Medulloblastoma, a common pediatric brain tumor, is a primitive neuroectodermal tumor which often displays neuronal and/or glial characteristics. We have investigated the consequences of treating cell lines derived from a human medulloblastoma with glia maturation factor-beta (GMF-beta), a protein found in mammalian brain. GMF-beta promotes growth arrest and morphological alteration of cultured glioma and neuroblastoma cells. The proliferation of medulloblastoma cells was arrested 24-48 hr after exposure to human recombinant GMF-beta. During the same period, treated cells acquired a morphology similar to that of mature astrocytes. By 72 hr, all treated cells bound an antibody against glial fibrillary acidic protein (GFAP), a distinguishing biochemical feature of mature astrocytes. Immunoreactivity was accompanied by de novo expression of GFAP mRNA. Our observations are the first demonstration of the induction of morphological and biochemical characteristics of mature astrocytes in cultured medulloblastoma-derived cells by an exogenous factor.

Establishment and characterization of four human medulloblastoma-derived cell lines.

We have established four cell lines, UW228-1, UW228-2, UW228-3 and UW443, from two posterior fossa medulloblastomas. The three UW228 sublines originated from a tumor with a diploid DNA content, while the tumor of origin of UW443 was predominantly tetraploid. Both tumors displayed areas of immunopositivity for synaptophysin and glial fibrillary acidic protein. All four cell lines have been grown as monolayers in continuous culture for 50 to 200 passages, are not contact inhibited at high density, and form colonies in soft agar. The UW228 sublines are aneuploid, have similar modal chromosome numbers, similar chromosomal duplications and identical marker chromosomes, and display loss of heterozygosity for identical sequences at the distal end of chromosome 17p. UW443 is diploid and also shows loss of heterozygosity for a distal sequence on chromosome 17p. All lines are immunopositive for two or more neurofilament proteins, three lines (UW228-1, UW228-2 and UW443) are immunopositive for synaptophysin, and none are immunopositive for glial fibrillary acidic protein. The lines differ in sensitivity to the alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. They also differ in dependence on the DNA repair protein O6-methylguanine-DNA methyltransferase for alkylating agent resistance and in levels of the DNA repair activities apurinic/apyrimidinic endonuclease and DNA polymerase beta. These properties establish UW228-1, UW228-2, UW228-3 and UW443 as four new, phenotypically distinct medulloblastoma-derived cell lines.