A four-gene LincRNA expression signature predicts risk in multiple cohorts of acute myeloid leukemia patients.

Prognostic gene expression signatures have been proposed as clinical tools to clarify therapeutic options in acute myeloid leukemia (AML). However, these signatures rely on measuring large numbers of genes and often perform poorly when applied to independent cohorts or those with older patients. Long intergenic non-coding RNAs (lincRNAs) are emerging as important regulators of cell identity and oncogenesis, but knowledge of their utility as prognostic markers in AML is limited. Here we analyze transcriptomic data from multiple cohorts of clinically annotated AML patients and report that (i) microarrays designed for coding gene expression can be repurposed to yield robust lincRNA expression data, (ii) some lincRNA genes are located in close proximity to hematopoietic coding genes and show strong expression correlations in AML, (iii) lincRNA gene expression patterns distinguish cytogenetic and molecular subtypes of AML, (iv) lincRNA signatures composed of three or four genes are independent predictors of clinical outcome and further dichotomize survival in European Leukemia Net (ELN) risk groups and (v) an analytical tool based on logistic regression analysis of quantitative PCR measurement of four lincRNA genes (LINC4) can be used to determine risk in AML.

The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning.

Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.

Blastomycosis presenting with prostatic involvement: report of 2 cases and review of the literature.

We report on 2 patients who presented with prostatic involvement as the first prominent clinical manifestation of systemic blastomycosis. The clinical symptoms of both patients began with dysuria and urinary retention. In 1 patient skin lesions developed 4 weeks later and the initial chest x-ray findings were positive. The other patient became aware of skin lesions concurrently with the urinary symptoms and had negative chest x-ray findings. Successful treatment consisted of amphotericin B in 1 case and ketoconazole in the other case. A review of the literature revealed 8 well documented cases of blastomycosis with the initial presenting symptom of prostatic involvement. A summary of the previously reported cases is presented and the importance of recognition of skin lesions in such patients is stressed.

Group b Streptococcal pneumonia in the elderly.

Group B streptococcal infections, although well studied in neonates, have only recently been appreciated as important infectious agents in adults. Seven cases of Group B streptococcal pneumonia were verified by transtracheal aspiration, blood and sputum cultures, or multiple stab cultures at autopsy. The infections were largely nosocomial and, ultimately, fatal in all seven patients. Our patients were older (average age, 73 years) and much more debilitated than the 13 cases reported in the literature. Diabetes was less common than previously reported. Previous antibiotic therapy was common. Concomitant isolation of another organism (especially Staphylococcus aureus) occurred in five patients. The morphologic findings at autopsy, in one patient, were characterized by a severely necrotizing destructive process. In our experience, Group B streptococcal pneumonia is more common, more devastating, and occurs in an older population than previously reported.