***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component , comprising cognitive decline and loss of cortical gray matter . We hypothesized that a neuroprotective/neurotrophic add-on strategy , recombinant human erythropoietin ( rhEPO ) in addition to stable antipsychotic medication , may be able to improve cognitive function even in chronic schizophrenic patients . Therefore , we design ed a double-blind , placebo-controlled , r and omized , multicenter , proof-of-principle ( phase II ) study . This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks . Chronic schizophrenic men ( N=39 ) with defined cognitive deficit ( ⩾1 s.d . below normal in the Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) ) , stable medication and disease state , were treated for 3 months with a weekly short ( 15 min ) intravenous infusion of 40 000 IU rhEPO ( N=20 ) or placebo ( N=19 ) . Main outcome measure was schizophrenia-relevant cognitive function at week 12 . The neuropsychological test set ( RBANS subtests delayed memory , language –semantic fluency , attention and Wisconsin Card Sorting Test ( WCST-64 ) – perseverative errors ) was applied over 2 days at baseline , 2 weeks , 4 weeks and 12 weeks of study participation . Both placebo and rhEPO patients improved in all evaluated categories . Patients receiving rhEPO  showed a significant improvement over placebo patients in schizophrenia-related cognitive performance ( RBANS subtests , WCST-64 ) , but no effects on psychopathology or social functioning . Also , a significant decline in serum levels of S100B , a glial damage marker , occurred upon rhEPO . The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia OBJECTIVE . Erythropoietin therapy is effective in decreasing transfusions to varying degrees in preterm infants . Recent animal studies using erythropoietin doses to achieve serum concentrations > 1000 mU/mL report neuroprotective effects . We evaluated the relationship between erythropoietin concentrations and neurodevelopmental outcome in extremely low birth weight infants . METHODS . Preterm infants who weighed ≤1000 g at birth were r and omly assigned to erythropoietin ( 400 U/kg 3 times per week ) or placebo/control . Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week . All infants  received supplemental parenteral and enteral iron . Peak serum erythropoietin concentrations were obtained every 2 weeks . Follow-up evaluation included anthropometric measurements , Bayley scales of mental and psychomotor development , neurologic examination , and determination of overall neurodevelopmental impairment . Data were collected at 18 to 22 months ' corrected age by certified examiners who were masked to the treatment group . Analyses were performed to identify correlations between erythropoietin concentrations and outcomes . RESULTS . Sixteen extremely low birth weight infants were enrolled ; 1 infant died at 2 weeks ( placebo/control ) , and 15 had erythropoietin concentrations measured ( 7 erythropoietin , 8 placebo/control ) . Peak erythropoietin concentrations were significantly different between groups during the study ( erythropoietin : 2027 ± 1464 mU/mL ; placebo/control : 26 ± 11 mU/mL ) . Before follow-up , 3 infants died ( 1 erythropoietin , 2 placebo/control ) , and 12 were available for follow-up ( 6 erythropoietin , 6 placebo/control ) . At 18 to 22 months ' follow-up , none of the erythropoietin recipients and 2 of the placebo/control infants had Mental Development Index scores < 70 . Erythropoietin recipients had Mental Development Index scores of 96 ± 11 , and placebo/control infants had Mental Development Index scores of 78 ± 7 . Psychomotor Development Index scores were similar between groups ( 87 ± 13 vs 80 ± 7 ) . There were no differences between groups with respect to anthropometric measurements . Two of 6 infants in the erythropoietin group and 4 of 6 infants in the placebo/control group had some form of neurodevelopmental impairment . Posthoc analysis showed that infants with erythropoietin concentrations ≥500 mU/mL had higher Mental Development Index scores than infants with erythropoietin concentrations < 500 mU/mL. CONCLUSIONS . Erythropoietin concentrations did not correlate with Psychomotor Development Index or overall incidence of neurodevelopmental impairment ; however , infants with elevated erythropoietin concentrations had higher Mental Development Index scores than those with lower erythropoietin concentrations . Close follow-up of infants who are enrolled in large , multicenter , high-dose erythropoietin studies is required to determine whether a correlation exists between elevated erythropoietin concentrations and improved neurodevelopmental outcome It is well known that epoetin alfa increases serum endothelin (ET)-1 and blood pressure . No data are available , however , on the effects of darbepoetin alfa on serum ET-1 and blood pressure . This study was conducted to compare the effects of darbepoetin alfa and epoetin alfa on serum ET-1 and blood pressure in patients on hemodialysis ( HD ) . A total of 42 patients on HD were included in the study . Serum sample s for measuring levels of ET-1 were taken 30 min after administration of epoetin alfa . After blood sample s had been taken from all patients , epoetin alfa was changed to darbepoetin alfa . Three months after the start of darbepoetin alfa treatment , blood sample s were taken to measure the same parameters . Mean arterial blood pressure was measured before recombinant human erythropoietin ( EPO ) administration and 30 min after EPO administration while patients were taking epoetin alfa or darbepoetin alfa . Injection of epoetin alfa or darbepoetin alfa significantly increased serum ET-1 levels compared with levels in those patients who were not on EPO therapy ( P < .05 ) . When the effects of epoetin alfa on serum ET-1 level were compared with those of darbepoetin alfa , the 2 types of EPO were found to increase serum ET-1 levels similarly ( P > .05 ) . Administration of epoetin alfa or darbepoetin alfa increased systolic and diastolic blood pressures significantly over values in the control group ( P < .05 ) . Serum systolic and diastolic blood pressures increased similarly after injection of epoetin alfa or darbepoetin alfa . Administration of darbepoetin alfa increased blood pressure in patients on HD in a way that was positively correlated with enhanced ET-1 release ; a similar correlation was noted with epoetin alfa BACKGROUND Anaemia is associated with poor cancer control , particularly in patients undergoing radiotherapy . We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer . METHODS We did a multicentre , double-blind , r and omised , placebo-controlled trial in 351 patients ( haemoglobin < 120 g/L in women or < 130 g/L in men ) with carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx . Patients received curative radiotherapy at 60 Gy for completely ( R0 ) and histologically incomplete ( R1 ) resected disease , or 70 Gy for macroscopically incompletely resected ( R2 ) advanced disease ( T3 , T4 , or nodal involvement ) or for primary definitive treatment . All patients were assigned to subcutaneous placebo ( n=171 ) or epoetin beta 300 IU/kg ( n=180 ) three times weekly , from 10 - 14 days before and continuing throughout radiotherapy . The primary endpoint was locoregional progression-free survival . We assessed also time to locoregional progression and survival . Analysis was by intention to treat . FINDINGS 148 ( 82 % ) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L ( women ) or 150 g/L ( men ) compared with 26 ( 15 % ) given placebo . However , locoregional progression-free survival was poorer with epoetin beta than with placebo ( adjusted relative risk 1.62 [ 95 % CI 1.22 - 2.14 ] ; p=0.0008 ) . For locoregional progression the relative risk was 1.69 ( 1.16 - 2.47 , p=0.007 ) and for survival was 1.39 ( 1.05 - 1.84 , p=0.02 ) . INTERPRETATION Epoetin beta corrects anaemia but does not improve cancer control or survival . Disease control might even be impaired . Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials Erythropoietin ( EPO ) is a c and i date compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis . The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia , aim ing at improvement of cognitive brain function as well as prevention/slowing of degenerative processes . Using rodent studies , primary hippocampal neurons in culture , immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man , we demonstrate that : ( 1 ) peripherally applied recombinant human ( rh ) EPO penetrates into the brain efficiently both in rat and humans , ( 2 ) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients , ( 3 ) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls , ( 4 ) rhEPO attenuates the haloperidol-induced neuronal death in vitro , and ( 4 ) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia . These observations , together with the known safety of rhEPO , render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance Recent research indicates that subjective well-being is a major determinant of medication compliance in schizophrenia . However , it is yet unresolved whether atypical neuroleptics differ regarding subjective side-effects . A self-report instrument has been constructed to evaluate ' subjective well-being under neuroleptics  ' ( SWN ) . The primary aims of the present study were to develop a short form of the SWN and to investigate the extent to which the atypical antipsychotic improves the patient 's subjective well-being . The short form of the SWN was constructed following an item analysis based on data from 212 schizophrenic patients medicated with either typical or atypical antipsychotics .  The short form of the SWN showed sufficient internal consistency and good construct validity . The SWN was only moderately correlated with positive and negative syndrome scale ( PANSS ) scores or changes in psychopathology ( r=-0.20 to -0.37 ) . SWN-ratings in patients receiving olanzapine were superior compared to those of patients medicated with either clozapine or risperidone on three of five domains of well-being . Clozapine reduced global psychiatric symptoms significantly more than risperidone . It is concluded that the assessment of subjective well-being under antipsychotic treatment provides an independent outcome measure which is relevant to compliance 
    Output:
    
The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment , such as neurotransmission regulation , neuroprotection , modulation of inflammation , effects on blood-brain barrier permeability , effects on oxidative stress and neurogenesis .
Several potentially detrimental side-effects of EPO therapy , such as increased risk of thrombosis , cancer , increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO .