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Elderly Skin ‘Raises Cancer Risk’

Older people are more at risk of skin cancer and infection because their skin is unable to mobilise the immune system to defend itself, UK research suggests.

It contradicts previous thinking that defects in a type of immune cell called a T cell were responsible for waning immunity with age.
Elderly skin 'raises cancer risk'
In fact, it is the inability of the skin to attract T cells to where they are needed that seems to be at fault.

The findings are published in the Journal of Experimental Medicine.

Study leader, Professor Arne Akbar from University College London, said reduced immunity in older people is well known, but why and how it happens is not.

“Going in to intervene may have consequences that we don’t realise and that’s where we need to do more research”says Professor Arne Akbar, study leader.

.

A number of volunteers – one group of 40-year-olds and one group aged over 70 – were injected with an antigen to stimulate an immune response from T cells.

As expected, the immune response in the older group was much less than that in the younger volunteers.

But when the researchers looked at the T cells there was nothing wrong with them.

What had declined in the older group was the ability of the skin to attract T cells – effectively the signals to direct them to the right place were missing.

Reversible

Further experiments with skin samples in a test tube showed that the skin was still able to send the appropriate signals when pushed, suggesting the problem is reversible.

“At the outset we thought it would be the cells responsible for combating infections that might be at fault, but the surprising thing was the T cells were fine but they couldn’t get into the skin – the signals were missing,” Mr Akbar said.

He said it raised the possibility of ways to boost the immune system in older people to give them a better chance of fighting infection and reducing the risk of skin cancer.

“The question that it raises is what survival advantage there is to this, is there a negative reason for having too much immunity in the skin when you get older?

“Going in to intervene may have consequences that we don’t realise and that’s where we need to do more research.”

He added that the same immune problems may be apparent in other tissues in the body.

Steve Visscher, deputy executive at the Biotechnology and Biological Sciences Research Council, which funded the research, said knowing more about the ageing process was vital as people increasingly live longer.

“The more knowledge we have about healthy ageing, the better we get at preventing, managing and treating diseases that are simply a factor of an ageing body.”

You may also click to see:-
>How flesh bug fools immune system
>Immune therapy Alzheimer’s hope
>Hope for test to measure ageing

Source: BBC NEWS: Aug.29 2009

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Green Tea is Good for Leukemia

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Mayo Clinic researchers are reporting positive results in early leukemia clinical trials using the chemical epigallocatechin gallate (EGCG), an active ingredient in green tea. The trial determined that patients with chronic lymphocytic leukemia can tolerate the chemical fairly well when high doses are administered in capsule form and that lymphocyte count was reduced in one-third of participants.

“We found not only that leukemia patients tolerated the green tea extract at very high doses, but that many of them saw regression to some degree of their chronic lymphocytic leukemia,” says Tait Shanafelt, lead author of the study. “The majority of individuals who entered the study with enlarged lymph nodes saw a 50 percent or greater decline in their lymph node size.”

Chronic lymphocytic leukemia is a type of cancer of the blood and bone marrow, the spongy tissue inside bones where blood cells are made.

The term “chronic” in chronic lymphocytic leukemia comes from the fact that it typically progresses more slowly than other types of leukemia. The “lymphocytic” in chronic lymphocytic leukemia comes from the cells affected by the disease, a group of white blood cells called lymphocytes, which help your body fight infection.

Chronic lymphocytic leukemia is the most common subtype of leukemia in the United States. Currently it has no cure. Blood tests have enabled early diagnosis in many instances; however, treatment consists of watchful waiting until the disease progresses. Statistics show that about half of patients with early stage diseases have an aggressive form of chronic lymphocytic leukemia that leads to early death. Researchers hope that EGCG can stabilize chronic lymphocytic leukemia for early stage patients or perhaps improve the effectiveness of treatment when combined with other therapies.

The research has moved to the second phase of clinical testing in a follow-up trial, already fully enrolled, and involving roughly the same number of patients. All will receive the highest dose administered from the previous trial.

These clinical studies are the latest steps in a multiyear bench-to-bedside project that began with tests of the green tea extract on cancer cells in the laboratory of Mayo hematologist Neil Kay, M.D., a co-author on this article. After laboratory research showed dramatic effectiveness in killing leukemia cells, the findings were applied to studies on animal tissues and then on human cells in the lab.

In the first clinical trial, 33 patients received variations of eight different oral doses of Polyphenon E, a proprietary compound whose primary active ingredient is EGCG. Doses ranged from 400 milligrams (mg) to 2,000 mg administered twice a day. Researchers determined that they had not reached a maximum tolerated dose, even at 2,000 mg twice per day.

Source:Eleminets4Health

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Ailmemts & Remedies

Cytopenia

DEFINITION:

Cytopenia is a reduction in the number of blood cells. It takes a number of forms:
*Low red blood cell count: anemia.
*Low white blood cell count: leukopenia or neutropenia (because neutrophils make up at least half of all white cells, they are almost always low in leukopenia).
*Low platelet count: thrombocytopenia.
*Low granulocyte count: granulocytopenia
*Low red blood cell, white blood cell, and platelet counts: pancytopenia..

Click to see the picture

Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

CLICK & SEE THE PICTURES

Cancer patients may frequently develop cytopenia, a disorder in which the production of one or more blood cell types ceases or is greatly reduced. Cancer and chemotherapy used to treat cancer, and sometimes radiation therapy, may sometimes cause cytopenia.

TYPES:
A deficiency of red blood cells which  is called anemia; a deficiency of white blood cells, or leukocytes, leukopenia or neutropenia (neutrophils make up over half of all white blood cells); and deficiency of platelets is called  thrombocytopenia.

Pancytopenia is the deficiency of all three blood cell types and is characteristic of aplastic anemia, a potentially life-threatening disorder that requires a stem cell transplant.

Blood Cells
The blood consists of three different  types of cells: red blood cells (erythrocytes), white blood cells (leukocytes), and platelets. Erythrocytes contain hemoglobin, the protein that carries oxygen from the lungs to all cells in the body. Proper cell function depends on an adequate oxygen supply. When cells are oxygen deprived, organ function can be seriously impaired.

Leukocytes (white blood cells) protect the body against viral, bacterial, and parasitic infection and detect and remove damaged, dying, or dead tissues. Someone with a deficiency of white blood cells is extremely vulnerable to infection.

The term “leukocyte” refers to all six types of white blood cells; each plays a unique role in the immune system:

1. Basophils circulate in the blood and initiate the inflammatory response.
2.Eosinophils kill infecting parasites and produce allergic reactions.
3.Lymphocytes produce antibodies and regulate immune responses.
4. Mast cells are fixed in tissues and initiate the inflammatory response.
5. Monocytes capture infecting organisms for identification, ingest infecting organisms, and remove damaged or dying cells and cell debris. When monocytes become fixed in tissue, they are called macrophages.
6.Neutrophils identify and kill infecting organisms, and remove dead tissue.

Platelets are essential factors for blood clotting. Sudden blood loss triggers platelet activity at the site of the wound. Exposure to oxygen in the air causes platelets to break apart and combine with a substance called fibrinogen to form fibrin. Fibrin has a thread-like structure and forms a scab, or external clot, as it dries. Platelet deficiency causes one to bruise and bleed easily. Blood does not clot at an open wound, and there is greater risk for internal bleeding.

All blood cells have a lifespan: erythrocytes have a lifespan of about 120 days; leukocytes, 1 to 3 days; and platelets, approximately 10 days. The body continually replenishes the blood supply through a process called hematopoiesis.

Blood Cell Formation—Hematopoiesis, the formation and development of blood cells, occurs in bone marrow. Bone marrow is a nutrient-rich spongy tissue located mainly in the central portions of long flat bones (e.g., sternum, pelvic bones) in adults and all bones in infants.

All blood cells derive from blood-forming stem cells that reside in bone marrow. Stem cells replicate indefinitely and develop into mature, specialized cells. A hormone produced in the kidneys, erythropoietin, stimulates blood stem cells to produce all three types of blood cells.

CAUSES & RISK FACTORS:-

Chemotherapy and radiation therapy both reduce the number of blood-forming stem cells in cancer patients, but chemotherapeutic agents have a greater adverse effect because they suppress bone marrow function in several ways.The degree of damage is related to the particular drug(s) and the dose.

Chemotherapeutic agents can produce deficiencies in all blood cell types by

* damaging blood-forming stem cells,
* suppressing the kidneys? production of erythropoietin (hormone that stimulates blood cell production), and
* triggering red cell destruction (hemolysis) by inducing an immune response that causes the body to mistakenly identify erythrocytes as foreign bodies and destroy them.

Malignant tumors can cause anemia and other cytopenias when they directly invade bone marrow and suppress marrow function. Malignant cells also can migrate from tumors in other parts of the body to bone marrow. Tumors also can replace normal blood-forming stem cells with abnormal clones.

SIGN & SYMPTOMS:-

Anemia
A deficiency in erythrocytes reduces the amount of oxygen reaching all cells in the body, thus impairing all tissue and organ function. Severe fatigue is the most common symptom of anemia and is experienced by approximately 75% of chemotherapy patients. Patients find it more disabling than other treatment side effects, including nausea and depression.

Anemia also produces these symptoms:

* Confusion
* Dizziness
* Headache
* Lightheadedness
* Loss of concentration
* Pallor (pale skin, nail beds, gums, linings of eyelids)
* Rapid heart rate (tachycardia)
* Shortness of breath (dyspnea)

Neutropenia
Patients with a white blood cell deficiency experience frequent and/or severe bacterial, viral, and/or fungal infections; fever; and mouth and throat ulcers.

Complications—Bacteremia, the form of sepsis characterized by the presence of bacteria in the blood, can develop in immunocompromised patients who have neutropenia. Fever, rapid heart rate, and quick shallow breathing are signs of early sepsis, usually a reversible condition.

Untreated bacteremia can lead to severe sepsis, in which one or more organs become dysfunctional. Septic shock is severe sepsis with low blood pressure. The risk for death increases with the development of septic shock. Even aggressive treatment can fail to reverse the condition.

Thrombocytopenia
Platelet deficiency causes patients to bruise and bleed easily. Bleeding occurs most often in the mucous membranes lining the mouth, nose, colon, and vagina. Tiny reddish-purple skin lesions (petechiae), evidence of pinpoint hemorrhages, may appear on the skin or in the mouth.

Pancytopenia
Patients who are deficient in all blood cell types experience signs and symptoms associated with each, but bleeding from the nose and gums, and easy bruising usually appear first. Symptoms of anemia (e.g., fatigue, shortness of breath) are also common. Patients may look and feel well, otherwise, despite the seriousness of their condition.

Anemia
People with anemia (reduced red cell production) are advised to rest and eat foods high in iron (meat, fish, poultry, lentils, legumes, iron-enriched grains and flours).

If immediate remedy is necessary, treatment may include medication that helps restore the red blood supply and a transfusion of packed red blood cells.

Epoetin alpha (Epogen®, Procrit®)is a synthetic erythropoietin (normally produced by the kidneys) that stimulates stem cells to produce red blood cells. Restoration of the red blood cell supply with medication is gradual.

Darbepoetin alfa (Aranesp®) also stimulates red blood cell production but requires fewer doses and less disruption of daily living.

In March 2007, the Food and Drug Administration (FDA) issued a warning about these medications in response to studies indicating that they may increase the risk for blood clots, strokes, and heart attacks in some patients (e.g., patients who have kidney disease).

Thrombocytopenia
People with an abnormally low platelet count should avoid bruising or breaking the skin, and should carefully brush their teeth. A persistently decreased platelet count may be treated with a transfusion of platelets.

Neutropenia
The patient with a low white blood cell count is advised to  do the following:

*Avoid contact with people who are ill,
*Monitor closely for signs of infection (e.g., fever), and
*Take antibiotics when appropriate.

Medication, a colony-stimulating factor (CSF), may be prescribed to speed the development of white blood cells and shorten the period of susceptibility to infection.

Growth Factors
Growth factors are synthetic versions of substances involved in stimulating red and white blood cell production. Physicians exercise caution when prescribing these medications for people with tumors that involve the bone marrow, because growth factors might stimulate malignant cell growth.

These medications include the following:

Epoetin alpha (Procrit®, Epogen®; stimulates red blood cell production)
G-CSF (granulocyte colony-stimulating factor; e.g., filgrastim [Neupogen®]; stimulates neutrophil production)
GM-CSF (granulocyte-macrophage colony-stimulating factor; stimulates production of several white blood cells, including macrophages)

Leukocytes and other cells that contain granules are also called granulocytes.

Side effects
Fever, fatigue, dizziness, diarrhea, nausea, vomiting, weakness, and paresthesia (prickling sensation) are side effects associated with epoetin alpha.

Bone pain, malaise, headache, flu-like symptoms, muscle ache, redness at the injection site, and skin rash may occur with GM-CSF.

G-CSF commonly produces bone pain.

MEDICATIONS:-

Medications used to treat bacterial infection and other illnesses also can contribute to immune system suppression.

Some of these are :

* Antacids: cimetidine (Tagamet®)
* Antibiotics: chloramphenical (Chloromycetin®), sulfonamide (Thiosulfil®, Gantanol®); cephalosporin (Cephalaxin®), vancomycin (Vancocin®)
* Anticonvulsants: phenytoin/hydantoin (Dilantin®), felbamate (Felbatol®), carbamazepine (Tegretol®)
* Antimalarials: chloroquine (Aralin®)
* Antivirals: ganciclovir (Vitrasert®), zidovudine (AZT®)
* Cardiac drugs: diltiazem (Cardizem®), nifedipine (Procardia®), verapamil (Calan®)
* Diabetes drugs: glipizide (Glucotrol®), glyburide (Micronase®)
* Hyperthyroid drug: propylthiouracil
* NSAIDs (nonsteroidal anti-inflammatory drugs): phenylbutazone (Butazolidine®), indomethacin (Indocin®, Indochron E-R®)—Due to potentially severe gastrointestinal and cardiovascular side effects, NSAIDs should only be used as instructed.
* Rheumatoid arthritis drugs: auranofin (Ridaura®), aurothioglucose (Solganal®), gold sodium thiomalate (Myochrisine®)

Bone Marrow and Stem Cell Transplantation:-
The treatment of choice for the pancytopenic patient with a matched bone marrow donor is stem cell transplantation. The goal of transplantation is to restore blood-forming stem cells to the marrow.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.oncologychannel.com/cytopenia/index.shtml
http://en.wikipedia.org/wiki/Cytopenia
http://www.cancer.umn.edu/cancerinfo/NCI/CDR378089.html

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Ailmemts & Remedies

Polycythemia

Definition:
Polycythemia is the increase of the RBC count, hemoglobin, and total RBC volume, accompanied by an increase in total blood volume. This must be distinguished from relative erythrocytosis secondary to fluid loss or decreased intake; this distinction can be made easily on a clinical basis. Polycythemia accompanies increased total blood volume, whereas relative erythrocytosis does not. Two basic categories of polycythemia are recognized:
...click to see…the picture..
* Primary polycythemias are due to factors intrinsic to red cell precursors and include the diagnoses of primary familial and congenital polycythemia (PFCP) and polycythemia vera (PV).
* Secondary polycythemias are caused by factors extrinsic to red cell precursors.

In normal hematopoiesis, myeloid stem cells give rise to erythrocytes, platelets, granulocytes, eosinophils, basophils, and monocytes. The production of each lineage is a function of cell proliferation, differentiation, and apoptosis. These various stages of differentiation rely on multiple interrelated processes. Protein growth factors, known as cytokines, stimulate proliferation of the multilineage cells (eg, interleukin [IL]-3, granulocyte-macrophage colony-stimulating activity [GM-CSF]). Other factors primarily stimulate the growth of committed progenitors (eg, GM-CSF, macrophage colony-stimulating factor [M-CSF], erythropoietin [Epo]).

Erythropoiesis is a carefully ordered sequence of events. Initially occurring in fetal hepatocytes, the process is taken over by the bone marrow in the child and adult. Although multiple cytokines and growth factors are dedicated to the proliferation of the RBC, the primary regulator is Epo. Red cell development is initially regulated by stem cell factor (SCF), which commits hematopoietic stem cells to develop into erythroid progenitors. Subsequently, Epo continues to stimulate the development and terminal differentiation of these progenitors. In the fetus, Epo is produced by monocytes and macrophages found in the liver. After birth, Epo is produced in the kidneys; however, Epo messenger RNA (mRNA) and Epo protein are also found in the brain and in RBCs, suggesting that some paracrine and autocrine function is present as well.  CLICK & SEE THE PICTURES

Erythropoiesis escalates as increased expression of the EPO gene produces higher levels of circulating Epo. EPO gene expression is known to be affected by multiple factors, including hypoxemia, transition metals (Co2+, Ni2+, Mn2+), and iron chelators. However, the major influence is hypoxia, including factors of decreased oxygen tension, RBC loss, and increased oxygen affinity of hemoglobin. In fact, Epo production has been observed to increase as much as 1000-fold in severe hypoxia.

Absolute polycythemia
The overproduction of red blood cells may be due to a primary process in the bone marrow (a so-called myeloproliferative syndrome), or it may be a reaction to chronically low oxygen levels or, rarely, a malignancy.

Primary polycythemia (Polycythemia vera)
Primary polycythemia, often called polycythemia vera (PCV), polycythemia rubra vera (PRV), or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow.  Often, excess white blood cells and platelets are also produced. Polycythemia vera is classified as a myeloproliferative disease. Symptoms include headaches, vertigo, and an abnormally enlarged spleen and/or liver. In some cases, affected individuals may have associated conditions including high blood pressure or the formation of blood clots. Transformation to acute leukemia is rare. Phlebotomy is the mainstay of treatment. A hallmark of polycythemia is an elevated hematocrit, with Hct > 55% seen in 83% of cases. Mutations in JAK2 are found in 95% of cases, though also present in other myeloproliferative disorders.

Secondary polycythemia
Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. In secondary polycythemia, there may be 6 to 8 million and occasionally 9 million erythrocytes per cubic millimeter (microliter) of blood. Secondary polycythemia resolves when the underlying cause is treated.

Secondary polycythemia in which the production of erythropoietin increases appropriately is called physiologic polycythemia. This physiologic (meaning normal) polycythemia is a normal adaptation to living at high altitudes (see altitude sickness). Many athletes train at high altitude to take advantage of this effect — a legal form of blood doping. Similarly, athletes with primary polycythemia may have a competitive advantage due to greater stamina.

Other causes of secondary polycythemia include smoking, renal or liver tumors, hemangioblastomas in the central nervous system, heart or lung diseases that result in hypoxia, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing’s syndrome. People whose testosterone levels are high because of the use anabolic steroids, including athletes who abuse steroids and people whose doctors put them on doses that are too high, as well as people who take erythropoietin may develop secondary polycythemia.

Secondary polycythemia can be induced directly by phlebotomy to withdraw some blood, concentrate the erythrocytes, and return them to the body.

Chuvash polycythemia
Chuvash polycythemia refers to a familial form of erythrocytosis different from classical polycythemia vera. This involved patients from Chuvashia and is associated with a C598T mutation in the von Hippel-Lindau gene (VHL).[6] A cluster of patients with Chuvash polycythemia have been found in other populations, such as on the Italian island of Ischia, located in the Bay of Naples.

Relative polycythemia
Relative polycythemia is an apparent rise of the erythrocyte level in the blood; however, the underlying cause is reduced blood plasma. Relative polycythemia is often caused by loss of body fluids, such as through burns, dehydration and stress.

Polycythemia vera
Earlier diagnostic criteria for polycythemia vera included the following (based on the Polycythemia Vera Study Group Diagnostic Criteria):1

* Red cell mass greater than 36 mL/kg for men and greater than 32 mL/kg for women
* Arterial oxygen saturation greater than 92%
* Splenomegaly or 2 of the following:
o Thrombocytosis greater than 400 X 109/L
o Leukocytosis greater than 12 X 109/L
o Leukocyte alkaline phosphatase activity greater than 100 U/L in adults (reference range, 30-120 U/L) without fever or infection
o Serum vitamin B-12 greater than 900 pg/mL (reference range, 130-785 pg/mL)
o Unsaturated vitamin B-12 binding capacity greater than 2200 pg/mL

The reference range for the clinician’s laboratory should be cross-correlated. The diagnostic criteria have undergone scrutiny and several revisions in recent years. In 2001, the World Health Organization (WHO) proposed a classification system for chronic myeloid neoplasms.2 The diagnosis of polycythemia vera fell under the broader category of chronic myeloproliferative diseases. This set of criteria quickly lost favor because of lack of validation3 and the discovery of JAK2 mutations in adult patients.4,5,6,7,8,9

Currently, the diagnosis of polycythemia vera is based on the 2008 WHO criteria, which has integrated molecular diagnostics into the evaluation and screening for polycythemia vera.10 A diagnosis of polycythemia vera is made when both major and one minor criterion are present or when the first major criterion is present with any two minor criteria.

The current criteria include the following:

* Major criteria
1. Hemoglobin level of more than 18.5 g/dL in men (>16.5 g/dL in women) or other evidence of increased red cell volume

or

Hemoglobin or hematocrit level higher than 99th percentile of method-specific reference range for age, sex, altitude, of residence

or

Hemoglobin level of more than 17 g/dL in men (>15 g/dL in women) if associated with a documented and sustained increase of at least 2 g/dL from an individual’s baseline value that can not be attributed to correction of iron deficiency

or

Elevated red cell mass greater than 25% above mean normal predicted value
2. Presence of JAK2V617F or similar mutation (eg, JAK2 exon 12 mutation)
* Minor criteria
1. Bone marrow trilineage myeloproliferation
2. Subnormal serum erythropoietin levels
3. Endogenous erythroid colony growth

Pathophysiology

Primary polycythemia

The disease is considered to be a form of the myeloproliferative syndromes that include polycythemia vera, essential thrombocythemia, agnogenic myeloid metaplasia, and myelofibrosis. The clonality of polycythemia vera is well established and was first demonstrated by Adamson et al in 1976.11 Subsequent studies suggest hypersensitivity of the myeloid progenitor cells to growth factors, including Epo, IL-3, SCF, GM-CSF, and insulinlike growth factor (IGF)–1, whereas other studies show defects in programmed cell death.

Until recently, the pathophysiology of polycythemia vera was unclear. In 2005, significant progress in the understanding of polycythemia vera was made with the discovery of an activating mutation in the tyrosine kinase JAK2 (JAK2V617F ), which now appears to cause most primary cases in adults.4,5,6,7,8 Several other mutations of JAK2 have since been described (eg, exon 12, JAK2H538-K539delinsI ).9,12 The JAK2 mutations are thought to possibly cause hypersensitivity to Epo via the Epo receptor, although the effects of this mutation remain to be fully characterized.

Familial clustering suggests a genetic predisposition. Whether these mutations are responsible for the development of polycythemia vera in pediatric patients is unclear. Some groups have reported lower rates of JAK2 mutations in children compared with adults,13,14,15 whereas other groups have seen similar rates with complete or near complete presence of JAK2V617F and other JAK2 mutations.12

PFCP is caused by a hypersensitivity of erythroid precursors to Epo. Several mutations (approximately 14) have been identified in the Epo receptor (EPOR) gene; however, EPOR mutations have not been identified in all PFCP kindreds. Most identified EPOR mutations (11) cause truncation of the c-terminal cytoplasmic receptor domain of the receptor. These truncated receptors have heightened sensitivity to circulating Epo due to a lack of negative feedback regulation.16

Secondary polycythemia

Secondary polycythemia may result from functional hypoxia induced by lung disease, heart disease, increased altitude (hemoglobin increase of 4% for each 1000-m increase in altitude), congenital methemoglobinemia, and other high–oxygen affinity hemoglobinopathies stimulating increased Epo production. Secondary polycythemia may also result from increased Epo production secondary to benign and malignant Epo-secreting lesions. Secondary polycythemia may also be a benign familial polycythemia.

Chuvash polycythemia, a congenital polycythemia first recognized in an endemic Russian population, has mutations in the von Hippel-Lindau (VHL) gene, which is associated with a perturbed oxygen dependent regulation of Epo synthesis.

Secondary polycythemia of the newborn is fairly common and is a result of either chronic or acute fetal hypoxia or delayed cord clamping and stripping of the umbilical cord.17
Frequency
United States

Primary polycythemia is rare; the overall prevalence of polycythemia vera is 2 cases per 100,000 people. The median age is 60 years. Only 0.1% of cases of polycythemia vera are observed in individuals younger than 20 years. Fewer than 50 cases of pediatric polycythemia vera have been reported in the literature. Secondary polycythemia is seen in 1-5% of all newborns in the United States.
International

Polycythemia vera has a similar incidence in Western Europe as in the United States, and occurrence rates are very low in Africa and Asia (as low as 2 cases per million per year in Japan).

Mortality/Morbidity
Death rates for children are unavailable. The complications found in polycythemia vera are related to 2 primary factors. The first includes complications related to hyperviscosity. The second involves bone marrow–related complications. Untreated, the median survival time for these patients is 18 months. However, if patients are treated, survival is greatly extended, as many as 10-15 years with phlebotomy alone. The causes of death in adults are as follows:

* Thrombosis/thromboembolism (30-40%)
* Acute myelogenous leukemia (19%)
* Other malignancies (15%)
* Hemorrhage (2-10%)
* Myelofibrosis/myeloid metaplasia (4%)
* Other (25%)

In the neonatal period, polycythemia-induced hyperviscosity can lead to altered blood flow and subsequently affect organ function. Infants with polycythemia are at increased risk for necrotizing enterocolitis, renal dysfunction, hypoglycemia, and increased pulmonary vascular resistance with resultant hypoxia and cyanosis. Although initially thought to cause neurologic dysfunction, the decrease in cerebral blood flow seen in newborns with polycythemia is a physiologic response and does not appear to cause cerebral ischemia.17
Race

In the United States, higher rates of polycythemia vera are observed in the Ashkenazi Jewish population, and lower rates are seen in blacks.
Sex

The male-to-female ratio is 1.2-2.2:1 in adults and 1:1 in children.
Age

The median age for polycythemia vera is 60 years. Only 0.1% of polycythemia cases occur in people younger than 20 years.
Clinical
History

The clinical features associated with polycythemia are a direct result of the increase in red cell mass, which causes an expansion of blood volume. Signs of hyperviscosity and increased metabolism accompany polycythemia. A thorough history must be obtained for a history of cardiac, pulmonary (including sleep apnea), hepatic or renal disease in the patient and a complete family history for evidence of familial polycythemia.

Symptoms include the following:

* Headache
* Weight loss
* Weakness or malaise
* Dizziness
* Pruritus
* Bruising
* Ruddy or red appearance of the skin
* Diaphoresis/dyspnea
* Visual disturbance
* Paresthesias
* Arthropathies
* GI – Fullness, thirst, abdominal discomfort, constipation

Physical

A thorough physical must be completed and include specific evaluation for signs and symptoms of underlying disease that may cause secondary polycythemia; it must include pulse oximetry, careful cardiac and pulmonary evaluation, and evaluation for signs of renal or hepatic disease.

Signs of polycythemia include the following:

* Rubor, especially facial rubor
* Skin plethora
* Hypertension, both systolic and diastolic
* Hepatomegaly
* Splenomegaly
* Conjunctival plethora (engorged vessels in the bulbar conjunctiva)
* Ecchymosis
* Cardiac hypertrophy (rarely observed)

Causes

* Primary polycythemia

o In the past, the pathophysiology was unclear, and primary polycythemias were thought to be due to both inherited and acquired mutations in erythroid progenitors, leading to abnormal red cell proliferation. However, in 2005, an activating mutation found in the tyrosine kinase JAK2 was implicated as the causative factor in polycythemia vera (PV). Five separate groups identified this mutation in approximately 80% (56-97% reported) of patients with polycythemia vera.
o This acquired V617F mutation in JAK2 leads to constitutively activated JAK2. Activated JAK2 induces erythropoietin (Epo) hypersensitivity; although not yet completely delineated, it is thought to act through an activating EPOR.
o Additional JAK2 mutations have been identified in exon 12,9 JAK2H538-K539delinsI ,18 and others.19
o Primary familial and congenital polycythemia (PFCP), which is commonly found to have mutations in the Epo receptor (EPOR) gene. Approximately 14 mutations have been identified.
* Secondary polycythemia
o Congenital causes include high affinity hemoglobin and 2,3-Bisphosphoglycerate (2,3-BPG) deficiency.
o Chuvash polycythemia, a congenital polycythemia first recognized in an endemic Russian population, has mutations in the von Hippel-Lindau (VHL) gene, which is associated with a perturbed oxygen-dependent regulation of Epo synthesis.
o Acquired causes included hypoxemia and Epo-secreting tumors.
o Polycythemia of the newborn usually results from a poor intrauterine environment or hypoxic insult during labor or delivery.

Treatment
Medical Care

* Primary polycythemia: The goals of therapy are to maximize survival while minimizing the complications of therapy as well as of the disease itself.
o Phlebotomy and myelosuppressive chemotherapy are the cornerstones of therapy and have produced a median survival time of 9-14 years after the beginning of treatment. The goal of phlebotomy is to maintain normal red cell mass and blood volume, with a target hematocrit of 45%. The mean survival time of adult patients treated solely with phlebotomy is 13.9 years; however, a high risk of thromboembolic complications is observed.
o In the past, patients have been treated with chlorambucil and other alkylating agents such as pipobroman and busulfan. However, these patients exhibited the highest rates of secondary malignancy including acute leukemia, lymphocytic lymphomas, and skin and GI carcinomas. The rates of malignancy appear lower with busulfan than with the other alkylating agents. Currently, these agents are rarely used.
o Patients treated with phosphorus-32 (32 P) tolerate treatment well and have prolonged periods of remission. However, these patients also exhibit increased rates of acute leukemias (10-15%). The mean survival time with32 P treatment is 10.9 years.
o Studies suggest that the use of interferon alfa decreases the need for phlebotomy and decreases the risk of thrombotic events. Its use is limited by side effects, cost, and route of administration.
o Recent studies using hydroxyurea as a myelosuppressive agent also show promise, reducing the need for phlebotomy. However, similarly to those treated with chlorambucil, these patients also experience higher rates of malignancy. Early clinical studies using imatinib are currently underway and are thus far inconclusive.
o Current recommendations for treatment of young patients rely primarily on phlebotomy because the thrombosis is far less likely to occur in children and the long-term risks of leukemia over a longer life span are increased.
o In the past, the use of anticoagulants, including antiplatelet drugs such as aspirin and dipyridamole (Persantine) had demonstrated increased risk of bleeding without an associated decrease in thrombotic events; therefore, anticoagulants have not previously been recommended. However, a large European study, results of which were published in the New England Journal of Medicine by Landolfi et al (2004),20 showed a decrease in thrombotic events in those patients receiving low-dose aspirin therapy and recommended aspirin therapy for those patients for whom no contraindications existed. This issue continues to remain under debate in the field of polycythemia treatment.
* Secondary polycythemia: Phlebotomy is used for symptomatic hyperviscosity. The goal is to treat the underlying cause of polycythemia.

Surgical Care
Surgery is not typically indicated. Occasionally, splenectomy is performed late in the course of the disease if massive splenomegaly causes adverse effects such as early satiety, anemia, or thrombocytopenia from sequestration.

Please note that these patients have a high risk of complications during surgical procedures.
Consultations

Consult a neurologist and neurosurgeon if evidence of a stroke is present.
Diet

Diet is unrestricted.
Activity

Contact sports and other activities should be limited for individuals in hypercoagulable and hypocoagulable states.
Medication

Current recommendations for treatment of young patients rely primarily on phlebotomy.
Antineoplastic agents

The following medications are not approved for pediatric polycythemia but are extrapolated from other pediatric treatment regimens, including leukemia and myelodysplastic syndrome.

Interferon alfa 2a and 2b (Roferon-A [alfa-2a], Intron A [alfa-2b])

A recombinant purified protein used IV for CML, hairy cell leukemia, and Kaposi sarcoma. Inhibits cellular growth and alters cell differentiation.

Dosing
Adult
CML: 9 million U/d IM/SC; initiate with 3 million U/d, increase by 3 million U every third day; not to exceed 9 million U/d
Pediatric: 2.5-5 million U/d IM/SC

Interactions:Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity.

Contraindictions : Documented hypersensitivity.

Precautions:
Pregnancy
C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus.

Precautions
Caution in brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS; use has been associated with depression, suicidal ideation and suicide attempts, and GI hemorrhage

Chlorambucil (Leukeran)
Antineoplastic alkylating agent of nitrogen mustard type used for CLL, giant follicular lymphoma, Hodgkin lymphoma, and lymphosarcoma.

Dosing:
Adult
0.1-0.2 mg/kg/d PO; adjust dose according to blood count

Pediatric
Not established; limited data available

Intractions:Live virus vaccines (eg, MMR) may result in severe or fatal infection when used in immunosuppressed patients

Contraindictions :Documented hypersensitivity; previous resistance to medication

Precautions:
Pregnancy
D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions
Caution in history of seizure disorders or current bone marrow suppression

Busulfan (Myleran)
Potent cytotoxic drug that, at recommended dosage, causes profound myelosuppression. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Dosing:
Adult
4-8 mg/d PO; may administer up to 12 mg/d; maintenance dosing range is 1-4 mg/d to 2 mg/wk; discontinue regimen when WBC reaches 10,000-20,000 cells/mL; resume therapy when WBC reaches 50,000/mL

Pediatric
0.06-0.12 mg/kg/d or 1.8-4.6 mg/m2/d PO; titrate dose to maintain WBC >40,000/mL; reduce dose by 50% if WBC is 30,000-40,000/mL; discontinue if WBC <20,000/mL

Pipobroman (Vercyte, Vercite)
The mechanism of action is not fully understood; however, the drug is considered to be an alkylating agent. Pipobroman has been used with some success for treatment of polycythemia vera and chronic granulocytic leukemia. The product was discontinued by the manufacturer in the United States in 1996 but is available in Europe.

Dosing
Adult

1 mg/kg/d PO initially for at least 30 d; if refractory, may increase to 1.5-3 mg/kg/d
Maintenance: 0.1-0.2 mg/kg/d PO; typically initiated when hematocrit has decrease by 50-55%
Pediatric

<15 years: Not established
>15 years: Administer as in adults

Follow-up
Inpatient & Outpatient Medications

* Allopurinol for hyperuricemia or gout
* Iron supplementation to manage the increased red cell production that may produce a functional iron deficiency that can cause red cell rigidity and increase the risk of stroke
* Folate
* Cimetidine for pruritus and upper GI distress

Complications

* Vascular occlusive events – Splenic infarcts, thrombosis (cerebral, portal vein, pulmonary embolus)
* Hemorrhage
* Marrow fibrosis resulting in pancytopenia
* Malignancy – Acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), lymphoma
* Hyperuricemia – Renal stones, nephropathy, gout
* Budd-Chiari syndrome

Prognosis

* The median survival time for patients with polycythemia vera (PV) is 18 months for untreated patients and 9-14 years for treated patients.

Patient Education

* Inform patients that they are prone to surgical complications and are at high risk in trauma situations secondary to coagulopathies.

Miscellaneous
Medicolegal Pitfalls<%2

Categories
Advice against Health Hazards

A/C in Car – Precautions

Do not turn on A/C immediately as soon as you enter the car. Open the windows after you enter your car and turn ON the air-conditioning after a couple of minutes.

click & see

According to a research done, the car dashboard, sofa, air freshener emits Benzene, a Cancer causing toxin (carcinogen – take note of the heated plastic Smell in your car).

In addition to causing cancer, it poisons your bones, causes anemia, and reduces white blood cells. Prolonged exposure will cause Leukemia, increasing the risk of cancer. May also cause miscarriage.

Acceptable Benzene level indoors is 50 mg per sq. ft… A car parked indoors with the windows closed will contain 400-800 mg of Benzene.
If parked outdoors under the sun at a temperature above 60 degrees F, the Benzene level goes up to 2000-4000 mg, 40 times the acceptable level… & the people inside the car will inevitably inhale an excess amount of the toxins.

It is recommended that you open the windows and door to give time for the interior to air out before you enter. Benzene is a toxin that affects your kidney and liver, and is very difficult for your body to expel this toxic stuff.

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