***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: To better estimate how frequently patients with low serum cobalamin ( Cbl ) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency , we prospect ively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period . Baseline hematologic , neuropsychiatric , and biochemical measurements were obtained , followed by a course of parenteral Cbl therapy and re assessment . A response to Cbl therapy was defined as one or more of the following : ( 1 ) an increase in hematocrit of 0.05 or more ; ( 2 ) a decrease in mean cell volume of 5 fL or more ; ( 3 ) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear ; and ( 4 ) an unequivocal and prompt improvement of neuropsychiatric abnormalities . Of the 300 patients with serum Cbl levels less than 200 pg/mL , 86 had one or more responses to Cbl therapy and 59 had no response . In 155 , insufficient data was available . In the Cbl-responsive patients , normal values were found for the following tests : hematocrit , 44 % ; mean cell volume less than or equal to 100 fL , 36 % ; white blood cell count , 84 % ; platelet count , 79 % ; serum lactic dehydrogenase , 43 % ; and serum bilirubin , 83 % . Peripheral blood smears were nondiagnostic in 6 % when review ed by the investigators , but 33 % as reported by routine laboratories . Serum Cbl levels in the 100 to 199 pg/mL range were present in 38 % . Neuropsychiatric abnormalities were noted in 28 % , often in the absence of anemia , macrocytosis , or both . Serum levels of methylmalonic acid and /or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94 % of the Cbl-responsive patients . We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency , even if anemia , an elevated mean cell volume , a marked depression of the serum Cbl , or other classic hematologic or biochemical abnormalities are lacking . Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency The concentration of blood folates was decreased and the concentration of plasma homocysteine was increased in a psychogeriatric population , whereas the concentrations of methylmalonic acid or serum cobalamins were not changed compared with healthy subjects . The highest frequency of abnormal values was shown by plasma homocysteine concentration , which was increased in 88 of 168 patients . In 29 of these 88 patients increased concentration of plasma homocysteine could possibly be attributed to tissue cobalamin deficiency . One patient had only a lowered concentration of blood folate . Thirteen patients had elevated concentrations of serum creatinine which could explain increased plasma homocysteine concentration . Even if the remaining patients ( n = 45 ) had normal vitamin levels in circulation , the increased plasma homocysteine concentration in most cases must be attributed to tissue deficiency of cobalamins and /or folates . Thus , many patients with increased plasma homocysteine concentrations need further vitamin supplementation despite their normal vitamin levels in serum and blood We report that  serum holotranscobalamin ( holoTC )  compares favorably with serum vitamin B12 for identifying vegans likely to have vitamin B12 deficiency as judged by measurements of the metabolites methylmalonic acid ( MMA ) and homocysteine ( tHcy ) . We also report that measurement of holoTC may possibly replace combined testing with serum vitamin B12 ( B12 ) , MMA , and tHcy in this population . Recently , two new markers for vitamin B12 deficiency , holoTC ( TC saturated with vitamin B12  ) and the related  TC saturation ( the fraction of total TC present as holoTC ) , have been introduced (1)(2)(3 ) . Approximately 30 % of circulating B12 is attached to TC , whereas the major part of B12 is attached to another protein , haptocorrin . Because only B12 attached to TC ( holoTC ) is able to enter all the cells of the body , holoTC may be a more useful marker than total B12 in serum . We compared  holoTC  with the tests currently used for diagnosis of vitamin B12 deficiency , i.e. , B12 , MMA , and tHcy , in vegan men , whose diets are devoid of food of animal origin ( and thus low in vitamin B12 ) and who thus are susceptible to developing B12 deficiency . The vegan men were recruited from two sources : 100 ( of a subset of 233 ) vegan men enrolled in the Oxford cohort of the EPIC study ( European Prospect i ve Investigation into Cancer and Nutrition ) between 1993 and 1997 for whom measurements of B12 had been performed at enrollment [ mean ( range ) B12 at enrollment , 170 ( 67–397 ) ng/L ; mean ( range ) age at recruitment , 49 ( 27–78 ) years ] ; and 72 men ( of a total of 96 respondents ) who were members of the London Vegan Society between 2001 and 2002 [ mean ( range ) age , 38 ( 18–70 ) years ] . The vegan men had consumed no food of animal origin for a mean ( range ) of 24 We measured the vitamin B-6 , vitamin B-12 , and folic acid nutritional status in a group of apparently healthy men ( n = 44 ) with moderate hyperhomocysteinemia ( plasma homocysteine concentration > 16.3 mumol/L ) . Compared with control subjects ( n = 274 ) with normal plasma homocysteine ( < or = 16.3 mumol/L ) concentrations , significantly lower plasma concentrations of pyridoxal-5'-phosphate ( P < 0.001 ) , cobalamin ( P < 0.001 ) , and folic acid ( P = 0.004 ) were demonstrated in hyperhomocysteinemic men . The prevalence of suboptimal vitamin B-6 , B-12 , and folate status in men with hyperhomocysteinemia was 25.0 % , 56.8 % , and 59.1 % , respectively . In a placebo-controlled follow-up study , a daily vitamin supplement ( 10 mg pyridoxal , 1.0 mg folic acid , 0.4 mg cyanocobalamin ) normalized elevated plasma homocysteine concentrations within 6 wk . Because hyperhomocysteinemia is implicated as a risk factor for premature occlusive vascular disease , appropriate vitamin therapy may be both efficient and cost-effective to control elevated plasma homocysteine concentrations OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels < or = 300 pg/mL , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > 3 SD ( 56 % ) compared with patients with low serum cobalamin levels ( < or = 200 pg/mL ) ( 62 % ) . Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospect ively . Results for complete blood count , lactate dehydrogenase , bilirubin , baseline neurologic score , and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites . The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment . One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment . CONCLUSION There was a high ( 14.5 % ) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly out patients . The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201 - 300 pg/mL compared with patients with low cobalamin levels ( < or = 200 pg/mL ) had markedly elevated metabolites which fell with cobalamin treatment . Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects OBJECTIVE To assess the prevalence of functional vitamin B12 deficiency status in an adult Jordanian seemingly healthy population . METHODS We carried out this study in the Department of Physiology , Faculty of Medicine , Jordanian University of Science and Technology , Jordan from September 2004 to January 2005 . We included a r and omly selected sample of 216 healthy adult volunteers ( male 124 , female 92 , aged 19 - 50 years ) from north Jordan . We carried out the measurement of hematological variables by Micros 60-OT Analyzer . We measured the  serum vitamin B12 by microparticle enzyme immunoassay and serum folate by ion-capture assay on an AxSYM Analyzer . RESULTS We found suboptimal ( < 222 pg/ml ) serum levels of vitamin B12 in 104 ( 48.1 % ) ( male 64 , female 40 ) subjects . The mean serum vitamin B12 level of male in all volunteers was 238.8 + /- 97.3 pg/ml , not significantly different ( p=0.24 ) from that of female ( 261.8 + /- 101.6 pg/ml ) . The mean serum values of vitamin B12 of male in the suboptimal group ( 168.3 + /- 36.4 pg/ml ; range 90 - 221 ) were not significantly different from that of female ( 178.2 + /- 27.5 pg/ml ; range 113 - 217 ) ( p=0.31 ) . Of the suboptimal group , 30 subjects ( 28.8 % ) had hyper-segmented neutrophils , 38 subjects ( 36.5 % ) had low mean corpuscular volume and 8 subjects ( 7.7 % ) had sub-optimal serum folate levels . CONCLUSION This study revealed that there was a high frequency of suboptimal serum vitamin B12 level , which is an early sign of negative B12 balance Abstract Early diagnosis of cobalamin deficiency is crucial , owing to the latent nature of this disorder and the result ing possible irreversible neurological damage . A normal serum cobalamin concentration does not reliably rule out a functional cobalamin deficiency and there does not at present seem to be any single diagnostic approach to achieve this diagnosis . A new marker for cobalamin status is the serum concentration of cobalamin bound to transcobalamin II ( holoTC ) . Because methods suitable for routine use have been unavailable until recently , the clinical value of lowholoTC is still uncertain . Furthermore , there is at the moment no gold st and ard or true reference method to diagnose subtle cobalamin deficiency , which makes evaluation of the clinical usefulness of holoTC and the estimation of sensitivity and specificity problematic . In this study , we aim ed to assess whether low holoTC concentrations are congruent with other biochemical signs of cobalamin deficiency in a group of psychogeriatric patients . The findings in the present study showthat holoTC is strongly related to serum cobalamin ( 0.68 ; p<0.001 in both patients and controls ) 
    Output:
    
From the available evidence , diagnosis of conditions amenable to cbl supplementation on the basis of serum cbl level alone can not be considered a reliable approach to investigating suspected vitamin deficiency