Marrow Bone

Bone disease Bone growth factor Bone imaging Bone marrow... 

Beckman Elutriation Method. The Beckman elutriation method uses a chamber designed so that the centrifugal effect of the radial inward fluid flow is constant (Fig. 3). The separation chambers are made of transparent epoxy resin which faciUtates observation of the movements of the cell boundary in strobe light illumination. This enables detection of the radius at which the cells are separating. When a mixture of cells, eg, mononuclear white cells, enters the chamber, separation can be achieved by fine tuning centrifuge speed and inward fluid flow to the specific cell group. This is a laboratory method suitable for relatively small numbers of cells. Chambers are available in sizes to handle 2-3 x 10 , 1 2 x 10 , and 1 x 10 ° cells. The Beckman chambers can be appHed to collect mononuclear cells from bone marrow aspirates. 

Pneumogstis carini pneumonia (PCP), the most common of the opportunistic infections, occurs in more than 80% of AIDS patients (13). Toxoplasmosis, a proto2oan infection of the central nervous system, is activated in AIDS patients when the 004 count drops and severe impairment of ceU-mediated immunity occurs. Typically, patients have a mass lesion(s) in the brain. These mass lesions usually respond well to therapy and can disappear completely. Fungal infections, such as CTyptococcalmeningitis, are extremely common in AIDS patients, and Histop/asma capsulatum appears when ceU-mediated immunity has been destroyed by the HIV vims, leading to widespread infection of the lungs, Hver, spleen, lymph nodes, and bone marrow. AIDS patients are particularly susceptible to bacteremia caused by nontyphoidal strains of Salmonella. Bacteremia may be cleared by using antibiotic therapy. 

Adverse side effects of gold treatments include stomatitis, rash, and proteinuria. Complete blood counts and urinalysis should be performed before each or every other injection of gold compounds. Pmritic skin rash and stomatitis are more common adverse effects that may resolve, if therapy is withheld for a few weeks and then restarted cautiously at a lower dose. Oral gold causes less mucocutaneous, bone marrow, and renal toxicity than injectable gold, but more diarrhea and other gastrointestinal reactions appear. 

GM-CSF, G-CSF, M-CSF, multi-CSF cytotoxic injury bone marrow transplantation myelodysplastic syndromes AIDS neutropenia rodent and human... 

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

Blood Access Devices. An investigational device called the Osteoport system allows repeated access to the vascular system via an iatraosseous iafusion directiy iato the bone marrow. The port is implanted subcutaneously and secured iato a bone, such as the iUac crest. Medications are adrninistered as ia any conventional port, but are taken up by the venous sinusoids ia the marrow cavity, and from there enter the peripheral circulation (8). 

A bone is classified according to shape as flat, long, short, or irregular. A living bone consists of three layers the periosteum, the hard cortical bone, and the bone marrow or cancellous bone. The periosteum is a thin coUagenous layer, filled with nerves and blood vessels, that suppHes nutrients and removes cell wastes. Because of the extensive nerve supply, normal periosteum is very sensitive. When a bone is broken, the injured nerves send electrochemical neural messages relaying pain to the brain. 

Technetium-99m albumin coUoid is cleared by the reticuloendothehal (RE) cells and is used for visualization of the RE system of the Hver, spleen, and bone marrow. The product is formed by the addition of up to 2.8 GBq (75 mCi) of Tc pertechnetate. 

Fig. 1. Hypothetical kinetics of depletion of bone marrow (BM) stem cells following exposure to a lethal total-body irradiation (TBI) of 10 Gy (1000 rad) of...

Hematology. The functional status of blood and of the blood-forming tissues can be assessed by tests which include red and white blood cell counts, platelet counts, clotting time, coagulation tests, and examination of bone marrow. Such tests, in addition to detecting abnormahties, may also allow differentiation between primary and secondary effects on blood and blood-forming tissues (75). 

Transport. Transcobalamin II dehvers the absorbed vitamin 3 2 to cells and is the primary plasma vitamin B22-binding transport protein. It is found in plasma, spinal fluid, semen, and extracellular fluid. Many cells, including the bone marrow, reticulocytes, and the placenta, contain surface receptor sites for the transcobalamin II—cobalamin complex. 

Dactinomycin, an antineoplastic dmg, was discovered in 1943 and is made in rather pure form by StreptomjcesparvuUus. Dactinomycin has some bacteriostatic antibacterial and antifungal activity, but high toxicity limits its use to antineoplastic therapy. It may be used alone or with other antineoplastics, with or without surgery and synergistic x-ray therapy. Dose limiting bone marrow toxicity may result in low white cell and platelet count. Intestinal mucosal damage also occurs. Reviews of more detailed chemotherapeutic information are available (217—222). 

Newer bleomycins such as peplomycin and especially liblomycin, are more resistant to bleomycin hydrolase. This results in less lung toxicity but more bone marrow toxicity, and allows for a different spectmm of antitumor action. Bleomycin is inactive orally it is given intravenously, intramuscularly, subcutaneously, or directiy into a cavity such as the pleural cavity. The majority of dmg is excreted unchanged in the urine. 

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

Trifluridine, C2qH22F2N20, (5-trifluoromethyl-2 -deoxyuridine [70-00-8] F TdU, 14) was first prepared (30) in 1962. It is used for topical therapy of herpes vims-infected eyes. It is especially usefiil for treating infections that are resistant to IdU therapy. Like IdU, trifluridine is incorporated into DNA in place of thymidine in both infected and uninfected cells. But it is 10 times more potent than IdU against herpes keratitis in rabbits and 10 times more soluble in water. Trifluridine is also usefiil in treating human cytomegalovims (HCMV), but its toxicity to bone marrow may limit its clinical use. 

Acyclovir is more effective the more serious the disease and the earher it is given. It has been shown to be efficacious when used systemicaHy in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephaUtis in humans (68). 

Another dideoxypyrimidine nucleoside active against human immunodeficiency vims is 3 -azido-2/3 -dideoxyuridine [84472-85-5] (AZDU or CS-87, 64) C H N O. Since its synthesis, (167) CS-87 has been identified as a promising antiHIV agent (168) and is currentiy undergoing phase I clinical trials in patients with AIDS and AIDS-related complex. It appears to be less potent than AZT against HIV in a peripheral blood mononuclear (PBM) cell screening system and in MT-4 cell lines. This lower activity in PBM cells appears to be related to a lower affinity of CS-87 for the enzyme responsible for its initial phosphorylation (169). However, CS-87 has significantly lower toxicity on bone marrow cells than AZT (170) and penetration of the CNS as a 5 -dihydropyridine derivative. 

Neither the mechanism by which benzene damages bone marrow nor its role in the leukemia process are well understood. It is generally beheved that the toxic factor(s) is a metaboHte of benzene (107). Benzene is oxidized in the fiver to phenol [108-95-2] as the primary metabolite with hydroquinone [123-31-9] catechol [120-80-9] muconic acid [505-70-4] and 1,2,4-trihydroxybenzene [533-73-3] as significant secondary metabolites (108). Although the identity of the actual toxic metabolite or combination of metabolites responsible for the hematological abnormalities is not known, evidence suggests that benzene oxide, hydroquinone, benzoquinone, or muconic acid derivatives are possibly the ultimate carcinogenic species (96,103,107—112). 

Recendy, the myelotoxicity has been proposed to occur through initial conversion of benzene to phenol and hydroquinone in the fiver, selective accumulation of hydroquinone in the bone marrow, followed by conversion of hydroquinone to benzoquinone via bone marrow myeloperoxidase. Benzoquinone is then proposed to react with macromolecules dismpting cellular processes (108). 

Acute benzene poisoning results in CNS depression and is characterized by an initial euphoria followed by staggered gait, stupor, coma, and convulsions. Exposure to approximately 4000 ppm benzene results in complete loss of consciousness. Insomnia, agitation, headache, nausea, and drowsiness may persist for weeks after exposure (126). Continued inhalation of benzene to the point of euphoria has caused irreversible encephalopathy with tremulousness, emotional lability, and diffuse cerebral atrophy (125). In deaths arising from acute exposure, respiratory tract infection, hypo- and hyperplasia of sternal bone marrow, congested kidneys, and cerebral edema have been found at autopsy. 

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