Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi.

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI(50)) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI(50) value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors.

Against all odds. Conservative management of Boerhaave's syndrome.

Spontaneous oesophageal perforation or Boerhaave's syndrome is a life-threatening condition that usually requires early diagnosis and early surgical management. A 79-year-old man presented to the accident and emergency department with an ischaemic left big toe. He reported a 2-week history of worsening symptoms and a claudication distance in his left leg of 20-30 m. Three days post-revascularisation of the leg, the patient reported chest pain radiating to the back. CT angiography of the aorta indicated Boerhaave's syndrome. Following 35 days of conservative management in the intensive care unit and high dependency unit, the patient was stepped down to a surgical ward. A water-soluble contrast study demonstrated minimal leak through the perforated oesophagus. The patient was started on oral intake, which was well tolerated. This case highlights that conservative management may be appropriate.

Re-occurrence of pancreatic insulinoma: an usual cause of hypoglycaemia.

A 42-year-old woman presented to her general practitioner (GP) with episodes of feeling 'shaky' exacerbated by physical exercise and prolonged fast. She was previously diagnosed with an insulinoma in 2006 (serum glucose 1.6 mmol/l, serum insulin 3.1 mIU/l and serum C peptide <165 pmol/l). CT abdomen/transabdominal ultrasound revealed a 1 cm insulinoma in the uncinate process of the pancreas and the patient later underwent pancreatic enucleation in 2006. Postpancreatic enucleation, 72 h fast was negative. The patient remained asymptomatic postoperation and re-presented to a locum GP 6 years later with initial symptoms. She was reviewed during her annual follow-up and, owing to concerns relating to her background, she was admitted to the specialist endocrine department for further investigations. A 72 h fast was positive for hypoglycaemia with serum glucose level 1.8 mmol/l, serum insulin 8.6 mIU/l and serum C peptide 443 pmol/l.

Fever, ulcers and joint pain: an incidental finding of oesophageal dysmotility.

A 41-year-old Bangladeshi man presented with a 2-month history of bilateral feet/hand swelling which intermittently resolved without medication. All blood tests performed by the general practitioner (GP) were unremarkable. Following admission to the accident and emergency department, a chest X-ray revealed a 'vail-like' opacification in the right side. High-resolution CT confirmed dilation of oesophagus with food debris and circumferential thickening of the lower oesophageal sphincter.

Never trust a croup...

A 2-year-old girl presented to the James Paget University Hospitals Trust with croup-like symptoms and was later discharged with dexamethasone syrup. The patient re-presented 6 h later following maternal concern with signs of acute respiratory distress. After a period of clinical stability, she acutely decompensated without any prior signs of a life-threatening deterioration. She was managed using nebulised epinephrine and showed signs of clinical improvement. Although improvement persisted, the child showed signs of exhaustion following the preceding events and was later intubed with an endotracheal tube and transferred to the paediatric intensive care unit at Addenbrooke's University Hospital, Cambridge. Endotracheal aspiration later grew parainfluenza virus, rhinovirus and Staphylococcus aureus and the patient was diagnosed with the exceptionally rare life threatening complications of croup, bacterial tracheitis. The patient was discharged from intensive care 7 days later and has since made a full recovery.

Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI50) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI50 value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors.