The Hematopoietic Syndrome

Gastrointestinal 10 Gy ( 1,000 rads) (some symptoms may occur as low as 6 Gy or 600 rads) 

Lymphocytopenia Symptoms are anorexia, nausea and vomiting. Onset occurs 1 h to 2 days after exposure. Stage lasts for minutes to days 

Abdominal pain, anorexia. Although patients may be Malaise, abdominal pain, 

In most cases, bone marrow cells begin to replicate full recovery for a large % of individuals from a few weeks up to 2 years after exposure. Death may occur in some patients at 1.2Gy (120rads) the LDjo,5o is about 2.5-5 Gy (250-500rads). Sepsis and hemorrhage are primary causes of death At doses greater than 12 Gy, mortality rate exceeds that of hematopoietic syndrome death due to infection, dehydration and electrolyte imbalance within 2 weeks of exposure the LD is about 10 Gy (1,000 rads) 

Nausea, vomiting, watery diarrhea, burning sensation of skin, disorientation, fever, extreme nervousness, confusion, impairment of cognitive function prostration, hypotension, ataxia and convulsions onset within minutes of exposure stage lasts for minutes to hours 

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Some skin damage frequently accompanies ARS. However, the cutaneous syndrome can also result from localized acute radiation exposure to the skin, usually from direct handling of radioactive sources or from contamination of the skin or clothes (2,8) (see Figs. 4.1 and 4.2) With localized exposure, even with high doses, the victim frequently survives, because the whole body usually does not receive the localized dose. However, if a patient with localized radiation induced cutaneous injury has also received whole body irradiation from an external source, the cutaneous damage increases the risk for death from the whole body exposure (2). Patients with the hematopoietic syndrome due to whole body irradiation will recover more slowly, if at all, from cutaneous injury due to bleeding, infection and poor wound healing (2). 

In addition, the documented radioprotectant activity of Cu(II)(3,5-DIPS)2 [505] is consistent with its anti-inflammatory activity [22, 84, 514], which relates to protection against the hematopoietic syndrome, its antiulcer activity [22, 84, 91, 514-516], which relates to its potential ability to protect against the gastrointestinal syndrome, and its anticonvulsant activity [324, 326, 516], which relates to its potential to protect against the central nervous system syndrome. 

Gastrointestinal (Gl) syndrome can result after acute exposure to 10 Gy or less. The radiation exposure causes destruction of the epithelial lining of the GI tract, and Gl syndrome is characterized by lethargy, diarrhea, dehydration, degeneration of bowel epithelium, and death in 10-14 days (NCRP, 1989). The other syndrome associated with acute exposure is hematopoietic syndrome, which may present days to weeks after total body radiation exposure ranging from 2.5 to 5 Gy. The hematopoietic syndrome is characterized by granulocytopenia, thrombocytopenia, hemorrhage, infection, and electrolyte imbalance. Even lower doses (1-5 Gy) can cause hematopoietic syndrome, which results in what... 

Various cytokines are required for the development of cell lineages in the hematopoietic system. Mainly, cytokines appear to act as survival factors to inhibit the apoptosis of these cells. The fact that hematopoietic stem cells in which apoptosis is suppressed by overexpressed Bcl-2 can differentiate in the absence of extracellular growth factors or cell division supports this hypothesis (T4). Myelodys-plastic syndromes and some forms of aplastic anemia are associated with increased apoptosis of hematopoietic stem cells (T4). 

L Severe combined immunodeficiency (SCID) syndromes are excellent models for gene therapy because of the genetic basis of these disorders and significant advances in the technology to transfer therapeutic genes into hematopoietic precursor cells. For all these reasons, which of the following syndromes represents an ideal candidate for gene therapy ... 

Identification of this gene rearrangement is the sine qua non for the diagnosis of CML, and its presence in the hematopoietic cells of virtually all patients with CML made it an ideal target for the development of therapeutic agents. Proof that BCR-ABL 1 was crucial for the development of CML was shown when the hybrid gene was transfected into bone marrow cells of mice which were subsequently transplanted into an irradiated syngeneic recipient and shown to lead to the development of a CML-like syndrome (5). 

The blood-forming organs are among the most sensitive to the effects of radiation, so these organs are among the first to show the results of high radiation exposure. Hematopoietic syndrome begins to appear at doses of... 

The presence of greater than normal amounts of thrombocytes in the circulation is known as thrombocytosis and along with reticulocytosis and leukocytosis is a manifestation of increased activity of the hematopoietic system. Zucker and Woodard (Z2) reported a series of 12 patients with thrombocytosis, consisting of two cases of polycythemia vera, three of essential thrombocytemia, three of chronic granulocytic leukemia, one myeloproliferative syndrome, one erythroleukemia, and one cancer of the bladder. The platelet counts ranged from 685 X 10 to 2500 X 10 per cubic millimeter, all much above the upper limit of normal. 

Table 4.2 illustrates the four distinct syndromes involving the hematopoietic, gastrointestinal and cerebrovascular systems. 

Whole-body Irradiation. Whole-body irradiation, where absorbed doses are high and acquired over short periods of time, will result in acute radiation sickness. There are three characteristic syndromes that make up the typical clinical pattern of acute radiation sickness. These are the hematopoietic, gastrointestinal, and neurovascular syndromes which occur with increasing dose, respectively. 

A. Hematopoietic Syndrome. Patients who have received doses of radiation in the low to mid-lethal range will have depression of bone-marrow function with cessation of blood-cell production leading to pancytopenia. Among treated patients, deaths should be minimal. 

Fligh doses of rifampin (greater than 600 mg) given once or twice weekly have resulted in a high incidence of adverse reactions including the following Flu-like syndrome hematopoietic reactions cutaneous, Gl, and hepatic reactions shortness of breath shock renal failure asymptomatic elevations of liver enzymes rash. Rifabutin... 

All sulfonamides, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, have been considered to be partially cross-allergenic. Flowever, evidence for this is not extensive. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract (see below). Stevens-Johnson syndrome, although relatively uncommon (ie, < 1% of treatment courses), is a particularly serious and potentially fatal type of skin and mucous membrane eruption associated with sulfonamide use. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances (see below), hepatitis, and, rarely, polyarteritis nodosa and psychosis. 

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