Cell-free tumour DNA testing for early detection of cancer - a potential future tool.

In recent years, detection of cell-free tumour DNA (ctDNA) or liquid biopsy has emerged as an attractive noninvasive methodology to detect cancer-specific genetic aberrations in plasma, and numerous studies have reported on the feasibility of ctDNA in advanced cancer. In particular, ctDNA assays can capture a more 'global' portrait of tumour heterogeneity, monitor therapy response, and lead to early detection of resistance mutations. More recently, ctDNA analysis has also been proposed as a promising future tool for detection of early cancer and/or cancer screening. As the average proportion of mutated DNA in plasma is very low (0.4% even in advanced cancer), exceedingly sensitive techniques need to be developed. In addition, as tumours are genetically heterogeneous, any screening test needs to assay multiple genetic targets in order to increase the chances of detection. Further research on the genetic progression from normal to cancer cells and their release of ctDNA is imperative in order to avoid overtreating benign/indolent lesions, causing more harm than good by early diagnosis. More knowledge on the sources and elimination of cell-free DNA will enable better interpretation in older individuals and those with comorbidities. In addition, as white blood cells are the major source of cell-free DNA in plasma, it is important to distinguish acquired mutations in leukocytes (benign clonal haematopoiesis) from an upcoming haematological malignancy or other cancer. In conclusion, although many studies report encouraging results, further technical development and larger studies are warranted before applying ctDNA analysis for early cancer detection in the clinic.

Diphenhydramine toxicity in three children with varicella-zoster infection.

Diphenhydramine hydrochloride is an antihistamine with anticholinergic properties that is frequently used both orally and topically for the temporary relief of pruritus. Significant systemic absorption may occur following topical administration of diphenhydramine in patients with varicella-zoster lesions. We describe three children with varicella-zoster infection (VZI) who developed bizarre behavior as well as visual and auditory hallucinations following topical applications of large amounts of diphenhydramine to the majority of skin surfaces. In two cases, oral diphenhydramine was also administered. Serum diphenhydramine concentrations approximated or exceeded those previously reported. In each case, a complete resolution of mental status abnormalities occurred within 24 hours after discontinuation of all diphenhydramine-containing products. Pharmacists and other health professionals should be aware of the potential toxicity of topical diphenhydramine in patients with VZI.

Use of surfactant in the prevention and treatment of neonatal respiratory distress syndrome.

The rationale for surfactant therapy in premature infants is presented, along with a discussion of the characteristics of surfactant and a review of clinical trials of surfactant for the prevention and treatment of neonatal respiratory distress syndrome (RDS). RDS is a major complication of prematurity, affecting up to 40,000 infants in the United States and Canada annually. Poor lung compliance due to a functional or quantitative deficiency of surfactant causes progressive collapse of the lungs. Surfactant, a mixture of phospholipids, neutral lipids, and proteins synthesized by pneumocytes during gestation, reduces surface tension and stabilizes alveoli, which increases lung compliance and decreases the work of breathing. Mammalian, human, and artificial surfactants are being investigated for use in premature infants. Several controlled trials of exogenous surfactant therapy have demonstrated reductions in mortality and pulmonary air-leak phenomena and improved gas exchange, but these results are not seen consistently, and no significant reductions in bronchopulmonary dysplasia have been observed. Surfactant has no appreciable toxicity, although the potential for immunogenicity exists. Typical doses range from 60 mg to 200 mg/kg administered endotracheally either before the first breath or after development of RDS. Surfactant is a safe investigational agent that appears promising for the prevention and treatment of neonatal RDS, although additional clinical trials with long-term follow-up are needed to determine its true efficacy.