Array-based karyotyping in plasma cell neoplasia after plasma cell enrichment increases detection of genomic aberrations.

The discovery of genomic abnormalities present in monoclonal plasma cells has diagnostic, prognostic, and disease-monitoring implications in plasma cell neoplasms (PCNs). However, technical and disease-related limitations hamper the detection of these abnormalities using cytogenetic analysis or fluorescence in situ hybridization (FISH). In this study, 28 bone marrow specimens with known PCNs were examined for the presence of genomic abnormalities using microarray analysis after plasma cell enrichment. Cytogenetic analysis was performed on 15 of 28 samples, revealing disease-related genomic aberrations in only 3 (20%) of 15 cases. FISH analysis was performed on enriched plasma cells and detected aberrations in 84.6% of specimens while array comparative genomic hybridization (aCGH) detected abnormalities in 89.3% of cases. Furthermore, aCGH revealed additional abnormalities in 24 cases compared with FISH alone. We conclude that aCGH after plasma cell enrichment, in combination with FISH, is a valuable approach for routine clinical use in achieving a more complete genetic characterization of patients with PCN.

Huffing-induced cardiomyopathy: a case report.

The intentional inhalation of fumes from gasoline or solvents for recreational purposes is commonly known as Huffing, Sniffing or Dusting (Anderson and Loomis in Am Fam Physician 68(5):869-874, 2003). Inhalant abuse is known to be "Cardio-toxic", causing sudden death and chronic myocardial damage (Meadows and Verghese in South Med J 89(5):455-462, 1996; Anderson and Loomis in Am Fam Physician 68(5):869-874, 2003). We report a 20-year-old white man who presented with altered mental status following ingestion of multiple alprazolam and oxycodone tablets. He was found to have diffused ST-T changes on his EKG. Cardiac enzymes were found to be elevated-CK: 599 U/L, CK-MB: 16.8 ng/mL and Troponin: 0.78 ng/mL. A transthoracic echocardiogram (TTE) revealed global left ventricular (LV) dysfunction with an ejection fraction (EF) of 10-15%. During hospitalization, the cardiac enzymes started trending downward and this was followed by spontaneous resolution of the LV dysfunction. The patient also admitted to inhaling "Dust-Off" spray 2-3 days prior to admission. Inhalant abuse can cause cardiomyopathy and should be considered a probable cause in patients presenting with cardiac dysfunction of unknown etiology, particularly in teenagers and young adults.

Detection of genomic abnormalities in multiple myeloma: the application of FISH analysis in combination with various plasma cell enrichment techniques.

Multiple myeloma (MM) is a hematopoietic neoplasm characterized by malignant plasma cells (PCs) that accumulate in the bone marrow. A number of different genomic abnormalities are associated with MM; however, detection of these by fluorescence in situ hybridization (FISH) can be limited by the percentage of PCs in the specimen. In this study, we tested 20 bone marrow specimens with known MM and a low concentration of monoclonal PCs for the presence of genomic abnormalities using FISH in combination with various PC enrichment techniques: magnetic cell sorting, targeted manual scoring, and automated image analysis. In addition, flow cytometric cell sorting of PCs in combination with FISH analysis was also tested for minimal residual disease applications. Different parameters were evaluated when assessing the detection efficiency of each approach. FISH results are highly dependent on the chosen enrichment method. We describe the evaluation of different techniques applicable for various laboratory settings and specimen parameters.

Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure.

Previous studies suggest that adenosine A1 receptor antagonists may promote natriuresis without deleterious effects on renal function. This study evaluated renal and hemodynamic effects as well as safety, pharmacokinetics, and tolerability of BG9928, a selective adenosine A1-receptor antagonist, in patients with heart failure. In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation study, 33 patients received a single dose of BG9928 (0.03, 0.3, 1.0, or 3.0 mg/kg) or placebo intravenously. Change from baseline in urinary sodium excretion for the 8-hour postdose interval was greater for all dosing groups versus placebo. The 0.03-mg/kg and 0.3-mg/kg groups had significant reductions in body weight versus placebo (-0.8 kg, -1.1 kg, 0.3 kg, respectively; P < 005). No changes in creatinine clearance or hemodynamic parameters were observed among any of the BG9928 groups versus placebo. However, pulmonary capillary wedge pressure tended to decrease and correlated with weight loss. Across the range of doses studied, pharmacokinetic parameters were linear and predictable. One patient who received the highest dose (3.0 mg/kg) developed seizures, and no further patients received that dose. Single intravenous BG9928 doses of up to 1.0 mg/kg were well tolerated and increased sodium excretion without worsening renal function. Further studies are needed to determine the clinical benefit of adenosine A1 receptor antagonism.

Demonstrating the impact of nutrition intervention in a heart failure program.

Outpatient heart failure centers using a multidisciplinary approach to management of heart failure are recognized as essential to decreasing costs of treating heart failure. These centers do not typically employ registered dietitians. With hospital foundation funding, our objective was to develop the role of the dietitian and to evaluate the impact of nutrition intervention in a multidisciplinary heart failure program. Based on a needs assessment, the dietitian developed and tested a medical nutrition therapy protocol, education materials, and special education projects. Unannounced 24-hour recalls at 3 points in time were used to determine changes in sodium and fluid intakes. An outcome tracking system was implemented. Intake data were analyzed for patients who were in the program 9 or more months (n = 79). Patients' sodium and fluid intakes at 2 to 3 months and 6 to 9 months were compared with their baseline intakes using paired t test. The sodium decrease of 0.5 g at 2 to 3 months and 6 to 9 months and the fluid decrease of 15 oz at 2 to 3 months and 12 oz at 6 to 9 months were all highly significant (P < .001). Patients active in year 3 (n = 82) completed the Minnesota Quality of Life Questionnaire. Compared with baseline, quality of life scores improved by 6.7 points (P < .003) at 3 months and by 5.9 points (P < .04) at 6 months. Of 83 patients hospitalized over 3 years, 6 hospitalizations were the result of an excessive sodium intake. At the completion of the project, the center provided funding for the dietitian to become a permanent team member. These positive findings indicate dietitians should seek involvement in heart failure centers.