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Most rails are secretive wetland birds that have made little cultural impression , but as a formerly common farmland bird with a loud nocturnal call that sometimes led to disturbed sleep for rural dwellers , the corn crake has acquired a variety of folk names and some commemoration in literature .
= = = Names = = =
The favoured name for this species among naturalists has changed over the years , with " <unk> " and variants of " corncrake " being preferred at various times . " Crake gallinule " also had a period of popularity between 1768 and 1813 . The originally Older Scots " <unk> " was popularised by Thomas Bewick , who used this term in his 1797 A History of British Birds . Other Scots names include " corn <unk> " and " <unk> " ; the latter term , like " king of the quail " , " grass quail " , the French " roi de caille " , and the German " <unk> " refer to the association with the small gamebird . Another name , " <unk> " , has been variously interpreted as onomatopoeic , or derived from the Old Norse ager @-@ <unk> , meaning " cock of the field " ; variants include " drake " , " drake Hen " and " gorse drake " .
= = = In literature = = =
Corn crakes are the subject of three stanzas of the seventeenth century poet Andrew Marvell 's " Upon Appleton House " , written in 1651 about the North Yorkshire country estate of Thomas Fairfax . The narrator depicts the scene of a mower cutting the grass , before his " whistling <unk> " unknowingly " carves the Rail " . The farmhand draws out the scythe " all bloody from its breast " and " does the stroke detest " . It continues with a stanza that demonstrates the problematic nature of the corn crake 's nesting habits :
John Clare , the nineteenth @-@ century English poet based in Northamptonshire , wrote " The Landrail " , a semi @-@ comic piece which is primarily about the difficulty of seeing corn crakes – as opposed to hearing them . In the fourth verse he exclaims : " Tis like a fancy everywhere / A sort of living doubt " . Clare wrote about corn crakes in his prose works too , and his writings help to clarify the distribution of this rail when it was far more widespread than now .
The Finnish poet Eino Leino also wrote about the bird in his poem " Nocturne " .
The proverbial use of the corn crake 's call to describe someone with a grating or <unk> voice is illustrated in the quotation " thanks to a wee woman with a voice like a corncrake who believed she was an apprentice angel " . This usage dates from at least the first half of the nineteenth century , and continues through to the present .
= Acute myeloid leukemia =
Acute myeloid leukemia ( AML ) , also known as acute <unk> leukemia or acute <unk> leukemia ( <unk> ) , is a cancer of the myeloid line of blood cells , characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells . AML is the most common acute leukemia affecting adults , and its incidence increases with age . Although AML is a relatively rare disease , accounting for roughly 1 @.@ 2 % of cancer deaths in the United States , its incidence is expected to increase as the population ages .
The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells , which causes a drop in red blood cells , platelets , and normal white blood cells . These symptoms include fatigue , shortness of breath , easy bruising and bleeding , and increased risk of infection . Several risk factors and chromosomal abnormalities have been identified , but the specific cause is not clear . As an acute leukemia , AML progresses rapidly and is typically fatal within weeks or months if left untreated .
AML has several subtypes ; treatment and prognosis vary among subtypes . AML is cured in 35 – 40 % of people less than 60 years old and 5 – 15 % more than 60 years old . Older people who are not able to withstand intensive chemotherapy have an average survival of 5 – 10 months .
AML is treated initially with chemotherapy aimed at inducing a remission ; people may go on to receive additional chemotherapy or a hematopoietic stem cell transplant . Recent research into the genetics of AML has resulted in the availability of tests that can predict which drug or drugs may work best for a particular person , as well as how long that person is likely to survive . The treatment and prognosis of AML differ from those of chronic <unk> leukemia ( <unk> ) in part because the cellular differentiation is not the same ; AML involves higher percentages of <unk> and undifferentiated cells , including more blasts ( <unk> , <unk> , and <unk> ) .
= = Signs and symptoms = =
Most signs and symptoms of AML are caused by the replacement of normal blood cells with leukemic cells . A lack of normal white blood cell production makes people more susceptible to infections ; while the leukemic cells themselves are derived from white blood cell precursors , they have no infection @-@ fighting capacity . A drop in red blood cell count ( anemia ) can cause fatigue , paleness , and shortness of breath . A lack of platelets can lead to easy bruising or bleeding with minor trauma .
The early signs of AML are often vague and nonspecific , and may be similar to those of influenza or other common illnesses . Some generalized symptoms include fever , fatigue , weight loss or loss of appetite , shortness of breath , anemia , easy bruising or bleeding , petechiae ( flat , pin @-@ head sized spots under the skin caused by bleeding ) , bone and joint pain , and persistent or frequent infections .
Enlargement of the spleen may occur in AML , but it is typically mild and asymptomatic . <unk> node swelling is rare in AML , in contrast to acute lymphoblastic leukemia . The skin is involved about 10 % of the time in the form of leukemia cutis . Rarely , Sweet 's syndrome , a paraneoplastic inflammation of the skin , can occur with AML .
Some people with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue . Rarely , the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow , called a <unk> . Occasionally , a person may show no symptoms , and the leukemia may be discovered incidentally during a routine blood test .
= = Risk factors = =
A number of risk factors for developing AML have been identified , including : other blood disorders , chemical exposures , ionizing radiation , and genetics .
= = = <unk> = = =
" <unk> " blood disorders , such as myelodysplastic syndrome ( MDS ) or myeloproliferative disease ( MPS ) , can evolve into AML ; the exact risk depends on the type of MDS / MPS .
= = = Chemical exposure = = =
Exposure to anticancer chemotherapy , in particular alkylating agents , can increase the risk of subsequently developing AML . The risk is highest about three to five years after chemotherapy . Other chemotherapy agents , specifically <unk> and anthracyclines , have also been associated with treatment @-@ related leukemias , which are often associated with specific chromosomal abnormalities in the leukemic cells .
Occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of AML . <unk> and many of its derivatives are known to be carcinogenic in vitro . While some studies have suggested a link between occupational exposure to benzene and increased risk of AML , others have suggested the attributable risk , if any , is slight .
= = = Radiation = = =
High amounts of ionizing radiation exposure can increase the risk of AML . Survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML , as did radiologists exposed to high levels of X @-@ rays prior to the adoption of modern radiation safety practices . People treated with ionizing radiation after treatment for prostate cancer , non @-@ Hodgkin lymphoma , lung cancer and breast cancer have the highest chance of acquiring AML , but this increased risk returns to the background risk observed in the general population after 12 years .
= = = Genetics = = =
A hereditary risk for AML appears to exist . Multiple cases of AML developing in a family at a rate higher than predicted by chance alone have been reported . Several congenital conditions may increase the risk of leukemia ; the most common is probably Down syndrome , which is associated with a 10- to 18 @-@ fold increase in the risk of AML .
= = Diagnosis = =
The first clue to a diagnosis of AML is typically an abnormal result on a complete blood count . While an excess of abnormal white blood cells ( <unk> ) is a common finding , and leukemic blasts are sometimes seen , AML can also present with isolated decreases in platelets , red blood cells , or even with a low white blood cell count ( leukopenia ) . While a presumptive diagnosis of AML can be made by examination of the peripheral blood smear when there are circulating leukemic blasts , a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy .
Marrow or blood is examined under light microscopy , as well as flow cytometry , to diagnose the presence of leukemia , to differentiate AML from other types of leukemia ( e.g. acute lymphoblastic leukemia - ALL ) , and to classify the subtype of disease . A sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent in situ hybridization . Genetic studies may also be performed to look for specific mutations in genes such as FLT3 , <unk> , and KIT , which may influence the outcome of the disease .
<unk> stains on blood and bone marrow smears are helpful in the distinction of AML from ALL , and in subclassification of AML . The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases . The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL . The nonspecific esterase stain is used to identify a <unk> component in <unk> and to distinguish a poorly differentiated <unk> leukemia from ALL .
The diagnosis and classification of AML can be challenging , and should be performed by a qualified <unk> or hematologist . In straightforward cases , the presence of certain morphologic features ( such as Auer rods ) or specific flow cytometry results can distinguish AML from other leukemias ; however , in the absence of such features , diagnosis may be more difficult .
The two most commonly used classification <unk> for AML are the older French @-@ American @-@ British ( FAB ) system and the newer World Health Organization ( WHO ) system . According to the widely used WHO criteria , the diagnosis of AML is established by demonstrating involvement of more than 20 % of the blood and / or bone marrow by leukemic <unk> , except in the three best prognosis forms of AML with recurrent genetic abnormalities ( t ( 8 ; 21 ) , <unk> ( 16 ) , and t ( 15 ; 17 ) ) in which the presence of the genetic abnormality is diagnostic irrespective of blast percent . The French – American – British ( FAB ) classification is a bit more stringent , requiring a blast percentage of at least 30 % in bone marrow ( BM ) or peripheral blood ( PB ) for the diagnosis of AML . AML must be carefully differentiated from " <unk> " conditions such as myelodysplastic or myeloproliferative syndromes , which are treated differently .
Because acute promyelocytic leukemia ( APL ) has the highest <unk> and requires a unique form of treatment , it is important to quickly establish or exclude the diagnosis of this subtype of leukemia . Fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose , as it readily identifies the chromosomal translocation [ t ( 15 ; 17 ) ( <unk> ; <unk> ) ; ] that characterizes APL . There is also a need to molecularly detect the presence of PML / <unk> fusion protein , which is an oncogenic product of that translocation .
= = = World Health Organization = = =
The WHO 2008 classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria . Each of the WHO categories contains numerous descriptive subcategories of interest to the <unk> and oncologist ; however , most of the clinically significant information in the WHO schema is communicated via categorization into one of the subtypes listed below .
The WHO subtypes of AML are :
Acute leukemias of ambiguous lineage ( also known as mixed phenotype or <unk> acute leukemia ) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells , or where both types of cells are present .
= = = French @-@ American @-@ British = = =
The French @-@ American @-@ British ( FAB ) classification system divides AML into eight subtypes , M0 through to M7 , based on the type of cell from which the leukemia developed and its degree of maturity . This is done by examining the appearance of the malignant cells with light microscopy and / or by using cytogenetics to characterize any underlying chromosomal abnormalities . The subtypes have varying prognoses and responses to therapy . Although the WHO classification ( see above ) may be more useful , the FAB system is still widely used .
Eight FAB subtypes were proposed in 1976 .
The morphologic subtypes of AML also include rare types not included in the FAB system , such as acute basophilic leukemia , which was proposed as a ninth subtype , M8 , in 1999 .
= = Pathophysiology = =
The malignant cell in AML is the myeloblast . In normal <unk> , the myeloblast is an immature precursor of myeloid white blood cells ; a normal myeloblast will gradually mature into a mature white blood cell . In AML , though , a single myeloblast accumulates genetic changes which " freeze " the cell in its immature state and prevent differentiation . Such a mutation alone does not cause leukemia ; however , when such a " differentiation arrest " is combined with other mutations which disrupt genes controlling proliferation , the result is the uncontrolled growth of an immature clone of cells , leading to the clinical entity of AML .
Much of the diversity and heterogeneity of AML stems is because leukemic transformation can occur at a number of different steps along the differentiation pathway . Modern classification schemes for AML recognize the characteristics and behavior of the leukemic cell ( and the leukemia ) may depend on the stage at which differentiation was halted .
Specific cytogenetic abnormalities can be found in many people with AML ; the types of chromosomal abnormalities often have prognostic significance . The chromosomal translocations encode abnormal fusion proteins , usually transcription factors whose altered properties may cause the " differentiation arrest " . For example , in acute promyelocytic leukemia , the t ( 15 ; 17 ) translocation produces a PML @-@ <unk> fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid @-@ specific genes and inhibits myeloid differentiation .
The clinical signs and symptoms of AML result from the growth of leukemic clone cells , which tends to displace or interfere with the development of normal blood cells in the bone marrow . This leads to neutropenia , anemia , and thrombocytopenia . The symptoms of AML are , in turn , often due to the low numbers of these normal blood elements . In rare cases , people with AML can develop a <unk> , or solid tumor of leukemic cells outside the bone marrow , which can cause various symptoms depending on its location .
An important pathophysiological mechanism of <unk> in AML is the epigenetic induction of <unk> by genetic mutations that alter the function of epigenetic enzymes , such as the DNA <unk> <unk> and the metabolic enzymes <unk> and <unk> , which lead to the generation of a novel <unk> , D @-@ 2 @-@ <unk> , which inhibits the activity of epigenetic enzymes such as <unk> . The hypothesis is that such epigenetic mutations lead to the silencing of tumor suppressor genes and / or the activation of proto @-@ oncogenes .
= = Treatment = =
First @-@ line treatment of AML consists primarily of chemotherapy , and is divided into two phases : induction and postremission ( or consolidation ) therapy . The goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level ; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure . <unk> stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses , although transplantation is also sometimes used as front @-@ line therapy for people with high @-@ risk disease . Efforts to use tyrosine kinase inhibitors in AML continue .
= = = Induction = = =
All FAB subtypes except M3 are usually given induction chemotherapy with cytarabine ( ara @-@ C ) and an anthracycline ( most often daunorubicin ) . This induction chemotherapy regimen is known as " 7 + 3 " ( or " 3 + 7 " ) , because the cytarabine is given as a continuous IV infusion for seven consecutive days while the anthracycline is given for three consecutive days as an IV push . Up to 70 % of people with AML will achieve a remission with this protocol . Other alternative induction regimens , including high @-@ dose cytarabine alone , FLAG @-@ like regimens or investigational agents , may also be used . Because of the toxic effects of therapy , including <unk> and an increased risk of infection , induction chemotherapy may not be offered to the very elderly , and the options may include less intense chemotherapy or palliative care .
The M3 subtype of AML , also known as acute promyelocytic leukemia ( APL ) , is almost universally treated with the drug all @-@ trans @-@ retinoic acid ( ATRA ) in addition to induction chemotherapy , usually an anthracycline . Care must be taken to prevent disseminated intravascular coagulation ( DIC ) , complicating the treatment of APL when the <unk> release the contents of their granules into the peripheral circulation . APL is eminently curable , with well @-@ documented treatment protocols .
The goal of the induction phase is to reach a complete remission . Complete remission does not mean the disease has been cured ; rather , it signifies no disease can be detected with available diagnostic methods . Complete remission is obtained in about 50 % – 75 % of newly diagnosed adults , although this may vary based on the prognostic factors described above . The length of remission depends on the prognostic features of the original leukemia . In general , all remissions will fail without additional consolidation therapy .
= = = Consolidation = = =
Even after complete remission is achieved , leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques . If no further postremission or consolidation therapy is given , almost all people with AML will eventually relapse . Therefore , more therapy is necessary to eliminate <unk> disease and prevent relapse — that is , to achieve a cure .
The specific type of postremission therapy is individualized based on a person 's prognostic factors ( see above ) and general health . For good @-@ prognosis leukemias ( i.e. <unk> ( 16 ) , t ( 8 ; 21 ) , and t ( 15 ; 17 ) ) , people will typically undergo an additional three to five courses of intensive chemotherapy , known as consolidation chemotherapy . For people at high risk of relapse ( e.g. those with high @-@ risk cytogenetics , underlying MDS , or therapy @-@ related AML ) , <unk> stem cell transplantation is usually recommended if the person is able to tolerate a transplant and has a suitable donor . The best postremission therapy for intermediate @-@ risk AML ( normal cytogenetics or cytogenetic changes not falling into good @-@ risk or high @-@ risk groups ) is less clear and depends on the specific situation , including the age and overall health of the person , the person 's values , and whether a suitable stem cell donor is available .
For people who are not eligible for a stem cell transplant , immunotherapy with a combination of histamine <unk> ( <unk> ) and interleukin 2 ( <unk> ) after the completion of consolidation has been shown to reduce the absolute relapse risk by 14 % , translating to a 50 % increase in the likelihood of maintained remission .
= = = <unk> AML = = =
For people with relapsed AML , the only proven potentially curative therapy is a hematopoietic stem cell transplant , if one has not already been performed . In 2000 , the monoclonal antibody @-@ linked cytotoxic agent <unk> <unk> ( <unk> ) was approved in the United States for people aged more than 60 years with relapsed AML who are not candidates for high @-@ dose chemotherapy . This drug was voluntarily withdrawn from the market by its manufacturer , Pfizer in 2010 .
Since treatment options for relapsed AML are so limited , palliative care or enrolment in a clinical trial may be offered .
For relapsed acute promyelocytic leukemia ( APL ) , arsenic trioxide is approved by the US FDA . Like ATRA , arsenic trioxide does not work with other subtypes of AML .