Better Outcome Of Disease Research Articles

Cardiac Echinococcosis

Abstract Hydatid disease has a worldwide distribution and can involve any body organ, though the liver and lung are most involved. Cardiac hydatid cysts are a rare occurrence and can cause fatal complications. Here, we discuss one such case of a 60-year-old female who presented with cough and expectoration with difficulty in breathing. On investigations, chest X-ray, and two-dimensional echocardiography, the presence of a cystic mass was noted in bilateral lung fields extending into the left atrium, and hence, the diagnosis of hydatid cyst was made. During her course of illness, the patient developed acute respiratory distress syndrome which was managed intensively, but the patient eventually succumbed to her illness. Postmortem examination confirmed the existence of a ruptured hydatid cyst in the left atrium. Early detection and treatment could have led to a better outcome of disease. Thus this case report highlights the importance of considering Hydatid disease as a differential for patients presenting with unexplained cardio-pulmonary symptoms especially in agriculture dependent areas of hydatid endemic nations.

Body Mass Index as a Predictor of Quality of life of Patients with Chronic Obstructive Pulmonary Disease

Background and Aim: Studies have reported that excessive weight and obesity are common in the early stages ofCOPD, and malnutrition is common in moderate and severe COPD. COPD is known to show “obesity paradox”i.e., obese and overweight COPD patients have better outcome of disease as compared to underweights. The aimof the study was to assess the BMI of COPD patients, its distribution and relationship with various factors.Material and Methods: Present study was conducted at tertiary care institute of India for the duration of oneyear. Total 400 COPD patients were selected to assess their body mass index (BMI) using Quetelet’s formula.Study subjects were selected using a systematic random sampling method. Study subjects were categorized as perWHO’s classification of BMI for Asian populations.Results: Out of a total of 400 subjects enrolled in the study, majority (49%) were obese followed by 35% overweightsand 7% underweights. Health-related quality of life of undernourished patients was most affected. A statisticallysignificant relation was seen across all the components of SGRQ.Conclusion: Present research established that, the disease related malnutrition is common in COPD patients,therefore, BMI might be a useful indicator to predict the prognosis of disease. This calls for an urgent need by ourprimary care physicians to provide simultaneous weight management interventions in COPD patients so as toimprove their nutritional status, enhance the strength of respiratory muscles and reduce the inflammation whichwill be effective in long-term management of the disease.

HIGH RESOLUTION CT IMAGING IN THE EVUALTION OF INTERSTITIAL LUNG DISEASES AND IT'S COMPARISION WITH CHEST X-RAY

Introduction: Interstitial lung disease( ILD) is one of the evolving disease that's needs to be diagnosed by various modalitites and treated in today's modern era. Some of the diseases are associated with signicant morbidity and mortality. Thus, we aimed to determine the radiological ndings of various Interstitial lung disease in HRCT Thorax and compare it with Chest x-ray to get a idea on how much chest x-ray and HRCT Thorax is effective in diagnosis of Interstitial lung disease for better outcome of disease. A cross sectional study was conducted on 120Method: patients with strong clinical suspicion of interstitial lung disease who were referred to the department of Radiodiagnosis, S.N Medical College Agra after taking detailed clinical history 120 patients underwent Chest X-ray and MDCT (64 Slice) examination of the thorax for evaluation of interstitial lung disease( ILD). Result: The main observation in our study was that higher number of patients with ndings were detected by HRCT thorax in comparision to Chest -Xray. We were able to detect higher no. of patients with ndings of septal thickenings, nodular opacities in HRCT Thorax in comparision to X-ray Chest and this difference between the two methods was found to be statistically signicant (P<0.05). We were able to detect higher no. of patients with ndings of reticular opacity, ground glass opacity, Traction bronchiectasis, honeycombing in HRCT Thorax in comparision to X-ray Chest and the difference between the two methods was not statistically signicant (P>0.05). The conclusion of this study is that HRCTConclusion: Thorax is much more sensitive than conventional chest radiography in the assessment and diagnosis of patients with interstitial lung diseases.

COVID-19 Management and Outcome of 76 Pediatric Cancer Patients, a Single Centre Experience from Developing Country

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic with no enough data regarding its impact on pediatric cancer patients. Our main aim is to describe the clinical management and outcome of COVID-19 in this vulnerable group. Methods: This prospective study included 76 pediatric oncology patients with confirmed infection in the period between 1st of May and end of November, 2020 with at least two-month follow-up from recruitment. Remdesivir (RDV) was the antiviral therapy used. Findings: The median age of patients was 9 years. Sixty patients were on first line treatment. Haematological malignancies constituted 86.8% of patients. Severe to critical form of infection represent 35.4% of cases. The commonest presentation was fever (93.4%). Chemotherapy was delayed in 59.2% of cases and doses were modified in 30.2%. Most acute lymphoblastic leukemia/lymphoblastic lymphoma (88%) were in maintenance treatment phase while 55% of acute myeloid leukemia were in induction phase. Sixty days overall survival (OS) was 86.6% and mortalities occurred only in critically ill cases. Of the sixteen acute leukemia who were in first induction phase, 13 survived and 10 achieved induction remission. The commonest CT chest finding was ground glass opacities (74.2%). A negative PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (p=0.008and, 0.002 respectively).Better OS was associated with regression of radiological finding after 30 days from infection (p=0.002). Of the forty-five cases who received RDV, 70% were severe to critically ill cases, yet morality was comparable to NoRDV with no serious adverse events observed. Interpretation: COVID-19 in pediatric cancer patients has good clinical outcome except for critical form of infection at presentation. New oncologic cases tolerate induction therapy with good disease outcome. RDS was well tolerated with no OS difference compared to patients who did not receive the drug.Funding: The present work was funded by the Children’s Cancer Hospital Foundation and Association of Friends of the National Cancer-free Initiative (AFNCI)Declaration of Interest: All authors declare no competing financial interests.Ethical Approval: The approval of hospital ethical committee and family consents were obtained.

Comprehensive study of morbidity in school going children in rural areas of western Rajasthan

Introduction: School age children (5-15 years) have not received as much attention from health providers/planners as the under fives. In India, several studies have been carried out on the health status of school age children. We have conducted to evaluate the extent and pattern of health status of school age children in village of Western Rajasthan by a mobile health team. Methods: This cross sectional epidemiological study was carried out in Osian block of Jodhpur district of Western Rajasthan over a period of one year. Medical officer and paramedical staff documented demographic and anthropometric data, including height, weight mid upper arm circumference, chest circumference, waist-circumference and blood pressure. Para medical staff was trained specifically for taking anthropometry and blood pressure in children. Results: Over a period of one year total 11651 children were screened. Dental carries was the most common problem followed by vision impairment and language delay (Table 1). Both males and females were equally affected (p >0.05). The overall intake of calories, iron, riboflavin, niacin and vitamin A was significantly less (p Conclusion: Educating the community about common diseases in children and their impact on the health of school age children, their etiology and prevention will go a long way in improving the quality of life of these children. By early detection and referral facility, there is less chances of complication of disease and better outcome of disease. Keywords: School age children, Dental caries, Anthropometry.

Parainfectious Transverse Myelitis secondary to Varicella Zoster Virus

Varicella zoster virus is a human herpes virus that causes chickenpox and herpes zoster. Varicella zoster virus leads to numerous complications of the central and peripheral nervous systems. Transverse myelitis is a disorder characterized by focal inflammation of the spinal cord and results in loss of motor and sensory function below the level of injury. Transverse myelitis caused by Varicella zoster virus reactivation is rare in immunocompetent patients. Herein, we report a case of transverse myelitis caused by Varicella zoster virus in an immunocompetent young patient. A 33 years gentleman was admitted to our hospital with complaints of multiple pleomorphic skin lesions and fever for 10 days, unable to pass urine on his will for four days and weakness of bilateral lower limbs for three days. MRI spine showed long segment ill-defined mild T2 hyper intensity noted in the spinal cord along the visible portion of lower thoracic vertebra. The patient was treated with steroids and Acyclovir.He recovered completely in one month after discharge. Prompt clinical diagnosis with early use of antiviral and anti-inflammatory treatment is important for good outcome of disease in resource limited country like Nepal.

Remyelination in multiple sclerosis: what do we know and where are we going?

Multiple sclerosis (MS) patients today have more hope of a good disease outcome with an ever-increasing choice of immunomodulatory therapies to reduce disease relapses, thought to be caused by inflammation within the CNS, leading to axonal demyelination. However, although there has been much progress in this disease phase, there has been little impact on the progressive phase of MS, when neurodegeneration dominates and patients accumulate disability over years. This failure of prevention of progressive disease has led to a frame-shift in research thinking, focusing on neuroprotective strategies such as promotion of remyelination, to be used alongside immunomodulatory therapies. This review discusses this unmet need in MS, in terms of pathology and current knowledge of remyelination and proremyelinating therapies.

S(+)-ibuprofen destabilizes MYC/MYCN and AKT, increases p53 expression, and induces unfolded protein response and favorable phenotype in neuroblastoma cell lines

Neuroblastoma is a common pediatric solid tumor that exhibits a striking clinical bipolarity favorable and unfavorable. The survival rate of children with unfavorable neuroblastoma remains low among all childhood cancers. MYCN and MYC play a crucial role in determining the malignancy of unfavorable neuroblastomas, whereas high-level expression of the favorable neuroblastoma genes is associated with a good disease outcome and confers growth suppression of neuroblastoma cells. A small fraction of neuroblastomas harbors TP53 mutations at diagnosis, but a higher proportion of the relapse cases acquire TP53 mutations. In this study, we investigated the effect of S(+)-ibuprofen on neuroblastoma cell lines, focusing on the expression of the MYCN, MYC, AKT, p53 proteins and the favorable neuroblastoma genes in vitro as biomarkers of malignancy. Treatment of neuroblastoma cell lines with S(+)-ibuprofen resulted in a significant growth suppression. This growth effect was accompanied by a marked decrease in the expression of MYC, MYCN, AKT and an increase in p53 expression in neuroblastoma cell lines without TP53 mutation. In addition, S(+)-ibuprofen enhanced the expression of some favorable neuroblastoma genes (EPHB6, CD44) and genes involved in growth suppression and differentiation (EGR1, EPHA2, NRG1 and SEL1L). Gene expression profile and Ingenuity pathway analyses using TP53-mutated SKNAS cells further revealed that S(+)-ibuprofen suppressed molecular pathways associated with cell growth and conversely enhanced those of cell cycle arrest and the unfolded protein response. Collectively, these results suggest that S(+)-ibuprofen or its related compounds may have the potential for therapeutic and/or palliative use for unfavorable neuroblastoma.

Exhaled breath condensate – from an analytical point of view

Over the past three decades, the goal of many researchers is analysis of exhaled breath condensate (EBC) as noninvasively obtained sample. A total quality in laboratory diagnostic processes in EBC analysis was investigated: pre-analytical (formation, collection, storage of EBC), analytical (sensitivity of applied methods, standardization) and post-analytical (interpretation of results) phases. EBC analysis is still used as a research tool. Limitations referred to pre-analytical, analytical, and post-analytical phases of EBC analysis are numerous, e.g. low concentrations of EBC constituents, single-analyte methods lack in sensitivity, and multi-analyte has not been fully explored, and reference values are not established. When all, pre-analytical, analytical and post-analytical requirements are met, EBC biomarkers as well as biomarker patterns can be selected and EBC analysis can hopefully be used in clinical practice, in both, the diagnosis and in the longitudinal follow-up of patients, resulting in better outcome of disease.

A65 The Studies of Autologous Stem Cells in Patients with a Prolonged Unconscious State after Traumatic Brain Injury

Mesenchymal stem cells (MSCs) - cells are pluripotent, residents of bone marrow stroma. MSCs сould be isolated from the bone marrow and in vitro could demonstrate a significant proliferative capacity. Recovery of nerve tissue and stimulation of angiognesis of the central nervous system (CNS) by MSC – is a modern, forward-looking method of treating patients in a prolonged unconsciousness state. Aim: To evaluate safety and efficacy of autologous mesenchymal stem (AMSK) bone marrow stromal cells in patients in extended unconscious state after traumatic brain injury. Materials and methods: a randomized study included 30 patients in unconscious state for more than 4 weeks after traumatic brain injury. 15 patients formed a control group, receiving standard therapy and 15 patients - experimental group, in which on a background of standard therapy we performed intravenous transplantation AMSK. Results: we did not observe any complications associated with the study within 6 months after AMSK transfusion in patients of experimental group. Within 12 months after injury, there was a good disease outcome (4–5 points on the Glasgow scale) in 5 patients in the control group and 4 patients of the experimental group. However, patients of the experimental group, regained consciousness, indicated a more rapid and better recovery of cognitive and motor function, compared with similar patients of the control group. A small number of patients and short time of observation does not allow us yet to make conclusions about the direct effect of AMSK on the recovery of consciousness, but neuroprotection and restoring of CNS probably occur more actively after the AMSK transplantation. Discussion: Our results of AMSK transplantation in patients with prolonged unconsciousness state after head injury can demonstrate the feasibility of using MSCs in the complex treatment of patients with severe CNS lesions. We have clearly marked such effects as stimulation of angiogenesis in the damaged areas of CNS, eliminating the defitiensy of macroergs in the CNS. All this showed the need for further research of stem cell transplantation in patients with severe damage to the CNS.

SPARC, FOXP3, CD8 and CD45 Correlation with Disease Recurrence and Long-Term Disease-Free Survival in Colorectal Cancer

BackgroundSPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3) protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC) stage, disease outcome and long-term cancer-specific survival (CSS) in stage II and III CRC.Methods and FindingsSPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS). Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p<0.0001). High SPARC expression correlated with good disease outcome (≥60 mths without disease recurrence, p = 0.0039) and better long-term CSS in stage II CRC (<0.0001). In stage III CRC, high SPARC expression correlated with better long-term CSS (p<0.0001) and less adjuvant chemotherapy use (p = 0.01). High FOXP3 correlated with a good disease outcome, better long-term CSS and less adjuvant chemotherapy use in stage II (p<0.0037, <0.0001 and p = 0.04 respectively), but not in stage III CRC. High CD8 and CD45RO expression correlated with better disease outcome in stage II CRC, and better CSS, but the differences were not as marked as for SPARC and FOXP3.ConclusionsThese data suggest that high SPARC and FOXP3 are associated with better disease outcome in stage II CRC and may be prognostic indicators of CSS. Further assessment of whether these markers predict patients at high risk of recurrence with stage II CRC and functional studies of these effects are underway

Effect of TRPV1 Blockade on Visceromotor Responses in Unanesthetized Rats With TNBS Colitis

GFP reporter mice, IL-23R-deficient mice lose weight during DSS treatment revealing a similar susceptibility to acute tissue injury. However, IL-23R-deficient mice gain weight during the recovery period with a better clinical score compared to IL-23R-GFP reporter mice. In particular, significant shortening and thickening of the colon with loose stools were observed in the IL-23R reporter mice. Analysis of IL-23R expressing cells revealed a reduced number of GFP positive cells in the MLN, colon IEL and LP of IL-23R-deficient mice as compared to IL-23R GFP reporter mice. IL-23R GFP expressing TCRαβ and TCRγδ T cells in the IL-23R GFP deficient mice were fewer compared to IL-23R reporter mice. Inflammatory cytokines IL-17 and IFN-γ were significantly reduced in IL23R deficient mice. Conclusions: IL-23R-deficient mice, although susceptible to DSS induced colitis, have a better outcome of disease than the IL-23R GFP reporter mice. This study suggests that IL-23R expressing cells contribute to the persistence and severity of inflammation after epithelial injury. The increase in the IL-23R expressing T cells observed in the IL-23R GFP reporter mice correlates with tissue inflammation

Biological significance of EPHA2 expression in neuroblastoma

Neuroblastoma is a pediatric solid tumor that exhibits striking clinical bipolarity. Despite extensive efforts to treat unfavorable neuroblastoma, survival rate of children with the disease is among the lowest. Previous studies suggest that EPHA2, a member of the EPH family receptor kinases, can either promote or suppress cancer cell growth depending on cellular contexts. In this study, we investigated the biological significance of EPHA2 in neuroblastoma. It was found that tumorigenic N-type neuroblastoma cell lines expressed low levels of EPHA2, whereas hypo-tumorigenic S-type neuroblastoma cell lines expressed high levels of EPHA2 (p<0.005). Notably, inhibitors of DNA methylation and histone deacetylase enhanced EPHA2 expression in N-type cells, suggesting that EPHA2 is epigenetically silenced in unfavorable neuroblastoma cells. Furthermore, ectopic high-level expression of EPHA2 in N-type neuroblastoma cell lines resulted in significant growth suppression. However, Kaplan-Meier survival analysis showed that high EPHA2 expression was not associated with a good disease outcome of neuroblastoma, indicating that EPHA2 is not a favorable neuroblastoma gene, but a growth suppressive gene for neuroblastoma. Accordingly, EPHA2 expression was markedly augmented in vitro in neuroblastoma cells treated with doxorubicin, which is commonly used for treating unfavorable neuroblastoma. Taken together, EPHA2 is one of the effectors of chemotherapeutic agents (e.g., gene silencing inhibitors and DNA damaging agents). EPHA2 expression may thus serve as a biomarker of drug responsiveness for neuroblastoma during the course of chemotherapy. In addition, pharmaceutical enhancement of EPHA2 by non-cytotoxic agents may offer an effective therapeutic approach in the treatment of children with unfavorable neuroblastoma.

Specific inhibition of NF-κB subunits prevents norepinephrine dependent, athero-thrombotic gene expression in experimental models of psychosocial stress

Aims: Disease-related psychosocial stress is common in patients with diabetes. Stress evoked elevated catecholamine levels have been shown to induce the redox-sensitive, proinflammatory transcription factor NF-κB, which is supposed to contribute to the pathogenesis of the micro and macrovascular late diabetic complications. Since most of the NF-κB inducers also trigger the release of radical oxygen species, antioxidants were supposed to effectively block NF-κB activation. Although certain studies have indicated beneficial effects of NF-κB inhibition, numerous recent reports have shown that long-term systemic inhibition of NF-κB does not lead to the better outcome of disease. This absence of beneficial effect of NF-κB lowering drugs in the prevention and therapy of diabetic vascular complications and atherosclerosis might be due to the parallel inhibition of NF-κB regulated protective genes. Therefore, we hypothesized that differential inhibition of defined NF-κB subunits might inhibit atherothrombotic gene expression, while preserving cellular defense mechanisms. Materials and methods: THP-1 cells were induced with 10nM norepinephrine (NE) in the presence or absence of pathway inhibitors. Subunit-specific NF-κB activation and expression of NF-κB regulated proatherogenic (ICAM-1, Tissue Factor (TF)) and protective(superoxide dismutase (MnSOD)) genes was studied using EMSA, Chromatin Immunoprecipitation, Western Blot and RT-PCR. Aortic tissue of ApoE-/–mice subjected to repeated restrain-stress were studied for atherosclerotic lesions and gene expression using Red Oil staining and immunohistochemistry. Results: Induction of THP-1 cells with 10nM NE or repeated restraint stress in ApoE-/-mice both resulted in increased binding of different NF-κB-subunits at the ICAM-1, TF and MnSOD-promoter and subsequent increase in mRNA synthesis and gene expression. While ICAM-1 was controlled by NF-κB subunits p50, p65 and cRel, TF expression was driven by p65/cRel. In contrast, MnSOD expression was dependent on binding of p50/p65 heterodimers. In vitro and in vivo nuclear translocation of NF-κBp50 was dependent on PKC-activation, NF-κBp65 was activated via p38MAPKinase and NF-κBcRel via the PI3/Akt pathway. Analysis of aortic tissue from ApoE-/–mice chronically stressed in the absence or presence of pathway inhibitors demonstrated that only inhibition of cRel resulted in reduction of atherosclerotic lesions. In contrast long time inhibition of neither NF-κBp50 nor NF-κBp65, both reducing MnSOD expression, had effects on vascular damage. Conclusion: NE induces differential activation of different NF-κB subunits that control proatherogenic, atherothrombotic and cellular defense mechanisms. Targeted and specific inhibition of NF-κB-subunits controlling proatherogenic gene expression, but not affecting cellular defence mechanisms, might therefore provide a future therapeutic option in the prevention and therapy of vascular complications in diabetes.

The Carcinoma–Stromal Ratio of Colon Carcinoma Is an Independent Factor for Survival Compared to Lymph Node Status and Tumor Stage

Background: Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP), as a derivative from the carcinoma-stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. Methods: In a retrospective study of 63 patients with colon cancer (stage I–III, 1990–2001) the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I–III, 1980–1992). (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy.) Results: Of 122 analyzed patients 33 (27.0%) had a low CP and 89 (73.0%) a high CP. The analysis of mean survival revealed: overall-survival (OS) 2.13 years, disease-free- survival (DFS) 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p < 0.0001, DFS p < 0.0001) with hazard ratio’s of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OSp < 0.001, OSp < 0.001). Conclusions: The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups.

Radiotherapy of inoperable brain tumors in childhood

Description and evaluation of radiotherapy of inoperable tumours of central nervous system. New possibilities in radiotherapy planning. Between 1987 and 2004, 58 patients (30 boys and 28 girls, mean age 8.5+/-4.3 years) with brain stem tumours were treated with 6 MV or 9 MV photons of the linear accelerator, or with telecobalt. The doses administered ranged from 30 to 71.2 Gy; mean 51.7+/-8.4 Gy. Treatment in each case was performed according to CT- and/or MR-based radiotherapy plan. As of 2000, in case of 16 patients a 3D conformal irradiation plan has been prepared. All patients were followed. The mean follow-up period was 21.8 months (range: 7 to 158 months). The mean duration of symptoms prior to diagnosis was 6.6+/-8.1 weeks (range: 1-52 weeks). Overall survival (OS) and progression-free survival (PFS) rates for all 58 patients were 39.9% and 21.2% at 1 years, 19.1% and 14.7% at 2 years, and 14.8% and 14.7% at 3 years respectively. The following factors were of prognostic influence on the OS in univariate analysis: duration of symptoms (< or = 2 months vs. >2 months, p=0.0081), radiological response (p < 0.0001) and clinical improvement (p = 0.0003). Prognostic factors for PFS were similar to those predicting for OS. Multivariate analysis revealed that the radiological (OS, p = 0.0034, PFS, p = 0.024) and clinical (OS, p = 0.026, PFS, p = 0.044) improvement 6 weeks after completion of radiotherapy were of prognostic significance. Accurate field arrangement, precise patient fixation, and CT- and MR-based 3D conformal radiotherapy planning may result in better outcome of disease as well as minimal effect on surrounding normal tissues. Radiotherapy should be provided also for histologically not verified tumours. Sixty-eight percent of these patients had a transitory 20.6-month improvement, and 12.1% of them completely recovered.

Implications of EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma.

Neuroblastoma (NB) is a common pediatric tumor that exhibits a wide range of biological and clinical heterogeneity. EPH (erythropoietin-producing hepatoma amplified sequence) family receptor tyrosine kinases and ligand ephrins play pivotal roles in neural and cardiovascular development. High-level expression of transcripts encoding EPHB6 receptors (EPHB6) and its ligands ephrin-B2 and ephrin-B3 (EFNB2, EFNB3) is associated with low-stage NB (stages 1, 2, and 4S) and high TrkA expression. In this study, we showed that EFNB2 and TrkA expressions were associated with both tumor stage and age, whereas EPHB6 and EFNB3 expressions were solely associated with tumor stage, suggesting that these genes were expressed in distinct subsets of NB. Kaplan-Meier and Cox regression analyses revealed that high-level expression of EPHB6, EFNB2, and EFNB3 predicted favorable NB outcome (P<0.005), and their expression combined with TrkA expression predicted the disease outcome more accurately than each variable alone (P<0.00005). Interestingly, if any one of the four genes (EPHB6, EFNB2, EFNB3, or TrkA) was expressed at high levels in NB, the patient survival was excellent (>90%). To address whether a good disease outcome of NB was a consequence of high-level expression of a "favorable NB gene," we examined the effect of EPHB6 on NB cell lines. Transfection of EPHB6 cDNA into IMR5 and SY5Y expressing little endogenous EPHB6 resulted in inhibition of their clonogenicity in culture. Furthermore, transfection of EPHB6 suppressed the tumorigenicity of SY5Y in a mouse xenograft model, demonstrating that high-level expressions of favorable NB genes, such as EPHB6, can in fact suppress malignant phenotype of unfavorable NB.

Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission.

Osteopenia is a typical finding in patients suffering from anorexia nervosa. Unfortunately, available longitudinal studies are limited by a relatively short follow-up period. Therefore cross-sectional long-term followup studies may help to determine both the outcome of this bone lesion and variables that influence its subsequent development. Of an initial 66 consecutive patients with anorexia nervosa, 51 (77.3%) could be further evaluated. After an average of 11.7 years following first admission, cross-sectional measurements of lumbar and proximal radial bone mineral density (BMD) were performed. The ability to predict BMD using variables obtained from anamnestic and clinical data was then determined by multiple-regression analysis. The BMD of both radial and lumbar bone in anorexic patients with poor disease outcome (as defined by the Morgan-Russell general outcome categories) deviated by -2.18 and -1.73 SD (Z score), respectively. In patients with a good disease outcome lumbar BMD was significantly less reduced compared with radial BMD (-0.26 versus -0.68 SD). Variables reflecting estrogen deficiency and nutritional status in the course of the disease, that is, relative estrogen exposure (for lumbar BMD) and years of anorexia nervosa (for radial BMD), allowed the best prediction of BMD. A marked reduction in cortical and trabecular BMD in anorexic patients with poor disease outcome suggests a higher risk of fractures in these patients. Furthermore, the finding of a persistently reduced cortical and a slightly reduced trabecular BMD, even in patients with good disease outcome, suggests that a recovery of trabecular BMD might be possible, at least in part. Recovery of cortical bone, if possible at all, seems to proceed more slowly.