scholarly journals Automated bone marrow analysis in rats- a change in paradigm in toxicologic clinical pathology?

2014 ◽  
Vol 43 (2) ◽  
pp. 121-122 ◽  
Author(s):  
Barbara von Beust
Keyword(s):  
Bone Marrow ◽  
Clinical Pathology ◽  
Bone Marrow Analysis

Loss of the Y Chromosome: An Age-Related or Clonal Phenomenon in Acute Myelogenous Leukemia/Myelodysplastic Syndrome?

2008 ◽  
Vol 132 (8) ◽  
pp. 1329-1332
Author(s):  
Anna K. Wong ◽  
Belle Fang ◽  
Ling Zhang ◽  
Xiuqing Guo ◽  
Stephen Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Y Chromosome ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Related Phenomenon ◽  
Patients Âgés ◽  
Age Related ◽  
Acute Myelogenous ◽  
Bone Marrow Analysis

Abstract Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease. Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS. Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age. Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group composed of 8 patients with complete loss of the Y chromosome in all karyotyped cells (1 case of AML and 7 cases of MDS). Conclusion.—Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.

scholarly journals Subchronic Oral Toxicity Study of Decitabine in Combination With Tetrahydrouridine in CD-1 Mice

2014 ◽  
Vol 33 (2) ◽  
pp. 75-85 ◽  
Author(s):  
Pramod Terse ◽  
Kory Engelke ◽  
Kenneth Chan ◽  
Yonghua Ling ◽  
Douglas Sharpnack ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Combination Therapy ◽  
Food Consumption ◽  
Blood Cells ◽  
Recovery Period ◽  
White Blood Cells ◽  
Clinical Pathology ◽  
High Dose ◽  
Severe Toxicity ◽  
Oral Toxicity

Decitabine (5-aza-2′-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia. A study was conducted in mice to assess safety of this combination therapy using oral gavage of DAC and THU administered 1 hour prior to DAC on 2 consecutive days/week for up to 9 weeks followed by a 28-day recovery to support its clinical trials up to 9-week duration. Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC. Doses were 167 mg/kg THU followed by 0, 0.2, 0.4, or 1.0 mg/kg DAC; THU vehicle followed by 1.0 mg/kg DAC; or vehicle alone. End points evaluated were clinical observations, body weights, food consumption, clinical pathology, gross/histopathology, bone marrow micronuclei, and toxicokinetics. There were no treatment-related effects noticed on body weight, food consumption, serum chemistry, or urinalysis parameters. Dose- and gender-dependent changes in plasma DAC levels were observed with a Cmax within 1 hour. At the 1 mg/kg dose tested, THU increased DAC plasma concentration (∼10-fold) as compared to DAC alone. Severe toxicity occurred in females receiving high-dose 1 mg/kg DAC + THU, requiring treatment discontinuation at week 5. Severity and incidence of microscopic findings increased in a dose-dependent fashion; findings included bone marrow hypocellularity (with corresponding hematologic changes and decreases in white blood cells, red blood cells, hemoglobin, hematocrit, reticulocytes, neutrophils, and lymphocytes), thymic/lymphoid depletion, intestinal epithelial apoptosis, and testicular degeneration. Bone marrow micronucleus analysis confirmed bone marrow cytotoxicity, suppression of erythropoiesis, and genotoxicity. Following the recovery period, a complete or trend toward resolution of these effects was observed. In conclusion, the combination therapy resulted in an increased sensitivity to DAC toxicity correlating with DAC plasma levels, and females are more sensitive compared to their male counterparts.

Bone marrow analysis of immune cells and apoptosis in patients with systemic lupus erythematosus

Lupus ◽  
2014 ◽  
Vol 23 (10) ◽  
pp. 975-985 ◽  
Author(s):  
JW Park ◽  
SY Moon ◽  
JH Lee ◽  
JK Park ◽  
DS Lee ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bone Marrow ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Bone Marrow Analysis

Isochromosome 12p mosaicism (Pallister-Killian syndrome): Newborn diagnosis by direct bone marrow analysis

1988 ◽  
Vol 31 (4) ◽  
pp. 835-839 ◽  
Author(s):  
Brian E. Ward ◽  
Melody W. Hayden ◽  
Arthur Robinson ◽  
John M. Opitz ◽  
James F. Reynolds
Keyword(s):  
Bone Marrow ◽  
Isochromosome 12P ◽  
Bone Marrow Analysis

Therapeutic Dilemma of Chemotherapy Dosing in Morbidly Obese Patient with AML: A Case Report and a Review of the Literature.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5534-5534
Author(s):  
Sakeer Hussain ◽  
Jonathan Glass ◽  
Oscar Ballester
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
White Male ◽  
Experimental Studies ◽  
Normal Karyotype ◽  
Induction Treatment ◽  
Morbidly Obese ◽  
High Dose ◽  
Obese Patients ◽  
Bone Marrow Analysis

Abstract Obesity is a common and increasing problem affecting the developed world. There is no consensus on a standard approach to chemotherapy dosing has been adopted in obese patients. We present a 25 year old white male with worsening fatigue, dyspnea and recurrent cellulites. Physical examination was significant for morbid obesity of 616 lb (BMI 86.4 and BSA 3.43m2). Initial laboratory values were WBC 0.870/ml (3400–9200/ml), Hb 6.5g/dL (11.5–15.4g/dl), platelet count of 35,000/mm3 (130000–400000/mm3), MCV 91 mm3 (80–100mm3). Basic metabolic and coagulation panel was normal except elevated D-dimer and LDH. Peripheral smear consistent with hypochromic normocytic RBC, occasional schistocytes, premature myeloid cells, myeloid blasts 26% with granularity of cytoplasm and a few Auer rods were evident. Bone marrow biopsy was consistent with acute myeloid leukemia. Flowcytometry was positive for CD33, CD 38 and myeloperoxidase. Lymphoid antigens were negative. Cytogenetic analysis revealed normal karyotype and negative for t (15; 17). Patient was treated with standard induction regimen with cytarabine 243mg (100mg/m2) and daunorubicin 109mg (45mg/m2). Chemotherapy dosing was done according to the adjusted body weight (BSA 2.43 m2). Day 14 bone marrow was consistent with significant disease. Reinduction with high dose cytarabine 14000mg (3000mg/m2) had no response. Patient was then received gemtuzumab ozagomycin 22mg (9mg/m2) on day 1 and 14. Bone marrow analysis 30 days after the treatment was consistent with remission. Interestingly patient developed little adverse effect from the initial induction chemotherapy. Hospital course was complicated with Clostridium difficile colitis and neutropenic fever which was treated with antibiotics and voricanazole. Voricanazole dosing was done according to the actual body weight (1000mg IV twice daily). The peak and trough levels were within normal range. Failed response to initial induction treatment could be due to refractory disease or inadequate dosing of chemotherapy in this patient. BSA has been used to calculate the dose in anticancer therapy since 1950s. Experimental studies have demonstrated BSA based dosing failed to standardize the variation in pharmacokinetics of cytotoxic drugs. In obese cancer patients, the pharmacokinetics of the drug demonstrated a prolonged elimination time for several agents. Risk of both under dosing and overdosing can have detrimental affect outcome in obese patients. Prospective studies of chemotherapy pharmacokinetics are needed to address the issue of optimal chemotherapy dosing in obese population.

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