Bone marrow dysfunction

Pre-existing bone marrow dysfunction and prolonged treatment is an important risk factor for toxic effects of thiamphenicol (20). 

On US, the pancreas with CF is characteristically of an echogenic texture secondary to fatty infiltration (Fig. 4.17). An enlarged pancreas may be seen initially with a subsequent atrophy later in life. Pancreatic duct dilatation and calcifications may be seen. Small cysts (anechoic areas) without vascular communication can be identified. Although a hyperechogenic pancreas is very typical of CF, some other diseases such as Schwachman-Diamond syndrome (exocrine pancreas insufficiency associated with bone marrow dysfunction, cyclic neutropenia, metaphyseal diastasis and growth retardation), hemosiderosis, chronic pancreatitis, and administration of steroids may also reveal this feature (Feigelson et al. 2000). 

The drug is contraindicated in die presence of an allergy to die drug, pregnancy (Category C), lactation, and phenylketonuria (oral form only). Linezolid is used cautiously in patients with bone marrow depression, hepatic dysfunction, renal impairment, hypertension, and hyperthyroidism. 

Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function. Immune dysfunctions appear to result from accumulation of dGTP and dATP, which inhibit ribonucleotide reductase and thereby deplete cells of DNA precursors. 

Carbamazepine Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug discontinue if platelets are less than 100,000/mm3, if white blood cell (WBC) count is less than 3,000/mm3 or if there is evidence of bone marrow suppression or liver dysfunction. Serum electrolyte levels should be monitored in the elderly or those at risk for hyponatremia. Carbamazepine interferes with some pregnancy tests. 

Familial demyelinative/dysmyelinative and axonal neuropathies may also be caused by impaired lysosomal lipid metabolism. Metachromatic leukodystrophy (sulfatide lipidosis) results from mutations of the arylsulfatase A gene, which encodes a lysosomal enzyme required for sulfatide turnover. Myelin is affected in both CNS and PNS, though dysfunction is restricted to the PNS in some patients, and the onset of symptoms can occur at any time between infancy and adulthood. Bone marrow transplantation can slow disease progression and improve nerve conduction velocities [57]. (See in Ch. 41.)... 

Disorders similar to CHS in humans have been reported in beige mice, Aleutian mink, Hereford cattle and killer whales, and neutrophil dysfunctions similar to those reported in humans are apparent in these animals. Therapy of CHS in humans usually consists of careful management of infections with appropriate antibiotics, although improvements have been reported following administration of high doses of ascorbic acid. Bone-marrow transplantation offers some hope to these patients, especially those entering the accelerated phase of the disease. 

Capsules/Tablets/Oral solution-There are significant adverse events caused by ribavirin capsules/interferon alfa-2b or peginterferon alfa-2b therapy, and ribavirin tablets/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. 

Concurrent leucovorin Trimetrexate must be used with concurrent leucovorin to avoid potentially serious or life-threatening complications, including bone marrow suppression, oral and Gl mucosal ulceration, and renal and hepatic dysfunction. Leucovorin therapy must extend for 72 hours past the last dose of trimetrexate. Inform patients that failure to take the recommended dose and duration of leucovorin can lead to fatal toxicity. Closely monitor patients for the development of serious hematologic adverse reactions. 

Antiproliferative compounds are easily detected using cell line or colonyforming unit (CPU) assays. Some of the potential mechanisms of non-antipro-liferative compounds leading to bone marrow toxicity include mitochondrial dysfunction [5, 6], aromatic hydrocarbon receptor (AhR) activation, receptor-mediated, altered receptor expression [7] and reactive intermediates [8, 9], but this list may grow with additional research as the mechanism(s) leading to bone marrow toxicity is still unknown for many compounds and will require significant amount of effort to elucidate. The next paragraphs briefly describe these potential mechanisms. 

The answer is C. The patient s symptoms represent a composite of neurologic and gastrointestinal dysfunction, which are consistent with the anemia that is due to lead poisoning. Testing for lead would be appropriate for the patient, the other members of the household, and the house itself. Inorganic lead produces the microcytic anemia by inhibition of heme synthesis in erythropoietic cells of the bone marrow. All the other options represent enzymes of heme synthesis or degradation, but none of them are affected by lead. 

Hepatic dysfunction and severe bone marrow suppression occur rarely. 

Trimetrexate given without concurrent leucovorin may result in serious or fatal hematologic, hepatic, and/or renal complications, including bone marrow suppression, oral and GI mucosal ulceration, and renal and hepatic dysfunction. 

Adverse effects include nausea, vomiting, diarrhoea, anaphylaxis, hepatic necrosis, fever, bone marrow depression, osteoporosis, menstrual dysfunction, cirrhosis, pulmonary infiltrates and fibrosis, renal toxicity and depigmentation. 

Adverse effects include depression of bone marrow which gives rise to leukopenia, thrombocytopenia, reticulocytopenia. GI disturbances, oral and anal ulceration, hepatic and renal dysfunction and peripheral neurotoxicity with high doses. 

Clinical pharmacology Erythropoietin is instrumental in the production of red cells from the erythroid tissues in the bone marrow. The majority of this hormone is produced in the kidney in response to hypoxia, with an additional 10% to 15% of synthesis occurring in the hver. Erythropoietin functions as a growth factor, stimulating the mitotic activity of the erythroid progenitor cells and early precursor cells. Chronic renal failure patients often manifest the sequelae of renal dysfunction, including anemia. Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. 

CBZ should not be used when there is a history of drug-induced hematological reactions bone marrow suppression hypersensitivity to this agent or other tricyclics and/or hepatic dysfunction. 

Because the onset of bone marrow suppression may be insidious, it is prudent to instruct patients to monitor themselves for the appearance of fever, malaise, sore throat, petechiae, or other evidence of possible hematological dysfunction rather than simply relying on periodic laboratory surveillance. In... 

Vinblastine is an alkaloid derived from the periwinkle plant Vinca rosea. Its mechanism of action involves inhibition of tubulin polymerization, which disrupts assembly of microtubules, an important part of the cytoskeleton and the mitotic spindle. This inhibitory effect results in mitotic arrest in metaphase, bringing cell division to a halt, which then leads to cell death. Vinblastine and other vinca alkaloids are metabolized by the liver P450 system, and the majority of the drug is excreted in feces via the biliary system. As such, dose modification is required in the setting of liver dysfunction. The main adverse effects are outlined in Table 54-4, and they include nausea and vomiting, bone marrow suppression, and alopecia. This agent is also a potent vesicant, and care must be taken in its administration. It has clinical activity in the treatment of Hodgkin s... 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

The chief toxic effect of azathioprine and mercaptopurine is bone marrow suppression, usually manifested as leukopenia, although anemia and thrombocytopenia may occur. Skin rashes, fever, nausea and vomiting, and sometimes diarrhea occur, with the gastrointestinal symptoms seen mainly at higher dosages. Flepatic dysfunction, manifested by very high serum alkaline phosphatase levels and mild jaundice, occurs occasionally, particularly in patients with preexisting hepatic dysfunction. 

Adverse Effects. The primary side effects of azathioprine are related to suppression of bone marrow function, including leukopenia, megaloblastic anemia, and similar blood dyscrasias. Other side effects include skin rash and gastrointestinal distress (appetite loss, nausea, vomiting) hepatic dysfunction can also occur when higher doses are used. 

Most common adverse effects include nausea, vomiting, diarrhea, abdominal pain, bone marrow depression with agranulocytosis, thrombocytopenia, and aplastic anemia. Cumulative toxicity is possible in elderly patients, hence it should be used cautiously. Care also should be exercised in patients with cardiac, hepatic, and renal dysfunctions. Colchicine causes teratogenicity in animals, and there are evidences of the risk of fetal chromosomal damage in humans. Colchicine should not be administered by the parenteral route as it causes severe local irritation. 

Furthermore, mouse model against Ehrlich s ascites tumour (EAT) [36]. This study showed that the treatment with ama-titano-cene 48 increases the lifespan of EAT-bearing mice from 25% to around 50% in a dose-dependent manner, and myelopoiesis (the formation of bone marrow or of blood cells derived from bone marrow) was not suppressed. Additionally, these experiments showed that ansa-titanocene 48 restores the natural killer cell function, which is reduced due to a dysfunction in EAT, and stimulates the natural killer cell-mediated cytotoxicity. 

Aplastic anaemia, manifesting itself by a fall of the number of red and white corpuscles, caused by the dysfunction of the bone marrow. Almost all of these cases end in death. 

Lewisite does not cause damage to the bone marrow or immunosuppression (Sidell et al, 1997). Arrhythmias and renal dysfunction are due to hypovolemia from fluid loss. Lewisite was fetotoxic to rats and rabbits and is a suspected carcinogen (Goldman and Dacre, 1989 RTECS, 2008). 

Recently ATIE concentrates have been used successfully for prophylaxis using continuous infusion for the bone marrow transplant (BMT) associated toxicity (52). Organ dysfunction during BMT has also been treated with ATIII concentrate (53). In the same... 

Antimetabolites cause gastrointestinal toxicity including stomatitis and diarrhoea as well as bone marrow depression renal impairment potentiates the toxicity of methotrexate. Active excreHon of methotrexate by the renal tubule is blocked by salicylate, which also displaces it from plasma protein, increasing the risk of toxicity. Hepatic dysfunction potentiates the toxicity of 5-fluorouracil, since it is primarily metabolised by the liver. 

Methotrexate Nausea and vomiting diarrhoea fever anaphylaxis hepatic necrosis Oral and gastrointestinal ulceration, perforation may occur bone marrow depression hepatic toxicity including cirrhosis renal toxicity pulmonary infiltrates and fibrosis osteoporosis conjunctivFtis alopecia depigmentation menstrual dysfunction encephalopathy infertility lymphoma teratogenesis... 

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