Widespread surgical emphysema following trivial injury to the hand.

A 23-year-old glazer presented to the A&E department with pain in his left arm following a 2 mm puncture injury to his left thenar eminence. Examination showed crepitus throughout the arm and over the chest wall. Plain X-rays confirmed extensive surgical emphysema but no evidence of pneumothorax. Clinical observations and laboratory markers for infection were normal. The patient was prescribed broad spectrum antibiotics for presumed gas-producing organism infection. After 24 h cultures returned negative and no other signs of infection were detected. Treatment was discontinued and the patient was allowed home. Several days later he experienced severe diarrhoea and as a result required time off work. No cause was found on investigation. We postulate a benign aetiology for the surgical emphysema in this case. In future it may be possible to recognise benign surgical emphysema at presentation and avoid prescribing unnecessary antibiotics.

Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in Acute Myeloid Leukaemia.

BACKGROUND: The CD34+CD38- subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment. METHODS: Chemosensitivity in phenotypically defined subsets from 34 primary AML samples was measured by flow cytometry following 48 hr in vitro treatment with gemtuzumab ozogamicin (GO, Mylotarg) and the farnesyltransferase inhibitor tipifarnib/zarnestra. The DNA damage response was measured using flow cytometry, immunofluorescence and immunohistochemistry. RESULTS: Using a previously validated in vitro minimal residual disease model, we now show that the combination of GO (10 ng/ml) and tipifarnib (5 µM) targets the CD34+CD38- subset resulting in 65% median cell loss compared to 28% and 13% CD34+CD38- cell loss in GO-treated and tipifarnib-treated cells, respectively. Using phosphokinome profiling and immunofluorescence in the TF-1a cell line, we demonstrate that the drug combination is characterised by the activation of a DNA damage response (induction of γH2A.X and thr68 phosphorylation of chk2). Higher induction of γH2AX was found in CD34+CD38- than in CD34+CD38+ patient cells. In a model system, we show that dormancy impairs damage resolution, allowing accumulation of γH2AX foci. CONCLUSIONS: The chemosensitivity of the CD34+CD38- subset, combined with enhanced damage indicators, suggest that this subset is primed to favour programmed cell death as opposed to repairing damage. This interaction between tipifarnib and GO suggests a potential role in the treatment of AML.