Hypertrophic Cardiomyopathy with a Twist.

Hypertrophic cardiomyopathy is a relatively common inherited cardiac disorder, with echocardiography still being the initial imaging method for its diagnosis. Cardiac fibroma is a primary neoplasm that most commonly presents in childhood. We present a patient who was investigated for typical cardiac symptoms who went on to have cardiac magnetic resonance imaging and was found to have both of these conditions.

A helix-loop-helix protein related to the immunoglobulin E box-binding proteins.

A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.

Evidence for a role for both the adenosine A1 and A3 receptors in protection of isolated human atrial muscle against simulated ischaemia.

OBJECTIVE: Adenosine receptor activation has been implicated in the mechanism of ischaemic preconditioning protection. Evidence suggests adenosine A1 receptor involvement, and possibly A3 receptor involvement in the rabbit. This study investigated the roles of these receptors in human preconditioning. Human A1- and A3-selective compounds were chosen based on Ki values for inhibition of N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA) binding to stably expressed recombinant human A1 and A3 receptors. Cyclopentyladenosine (CPA), a 194-fold selective A1 agonist, and iodobenzylmethylcarboxamidoadenosine (IBMECA), a 10-fold selective A3 agonist were used alone and in combination with dipropylcyclopentylxanthine (DPCPX) a 62-fold selective A1 antagonist. METHODS: Human atrial trabeculae were superfused with oxygenated Tyrode's solution. After stabilisation, muscles underwent one of 8 protocols (n = 6 per group), followed by 90 min of simulated ischaemia and 120 min of reoxygenation. The experimental endpoint was recovery of contractile function, presented as percentage baseline function. RESULTS: 5 nM CPA (52.2 +/- 3.1%), 30 nM IBMECA (49.7 +/- 3.8%) and preconditioning (55.3 +/- 2.5%) produced similar functional recoveries at 120 min of reoxygenation; significantly different to controls (27.7 +/- 1.0%; P < 0.05, ANOVA). When DPCPX (200 nM) was added prior to 5 nM CPA, protection was lost (31.8 +/- 0.9%), but when added prior to 30 nM IBMECA, muscles continued to be significantly protected (41.5 +/- 2.3%). CONCLUSIONS: In human atrium both A1 and A3 receptor stimulation appears to mimic ischaemic preconditioning. This may represent the first evidence for A3 receptor involvement in 'pharmacological' preconditioning of human myocardium.

Intraluminal biopsy of a superior vena cava mass.

A number of methods have been devised for the biopsy of intracaval tumour masses but all risk damage to the cava and tumour dissemination. We report on a case in which the tumour mass was almost entirely within the superior vena cava and describe an 'endoscopic' technique for biopsy.

An unusual presentation of acute lumbar nerve root pain. A case report.

STUDY DESIGN: This case report illustrates the need to be vigilant of potential iatrogenic causes of symptoms. A patient with a femoral Hickman line experienced severe back pain after a chemotherapy infusion commenced and developed a right quadriceps weakness and absent knee jerk. OBJECTIVES: To highlight the severe side effects possible with the use of Hickman lines and chemotherapy. SUMMARY OF BACKGROUND DATA: There are numerous causes of lumbar radicular pain, and these can coexist in the same patient. This patient had a known malignant process involving the retroperitoneum, but the actual cause of the severe pain related to the management of the malignancy rather than the malignancy itself. There are no reported cases of such a complication from a Hickman line. METHODS: This patient was admitted to hospital for investigation and treatment of severe back pain after the start of a continuous infusion of chemotherapy for an inoperable cholangiocarcinoma. The patient went on to develop a right quadriceps weakness before the investigations could reveal the cause of the problem. RESULTS: the pain and weakness resolved after cessation of the infusion and removal of the Hickman line. CONCLUSIONS: The principles of clinical medicine involve careful history taking and examination and considering all the differential diagnoses fully. Also, the possibility of multiple pathology and iatrogenic causes should be assessed. This patient was receiving palliative treatment only, and this unfortunately led to additional disability, which may have been avoidable or less severe.

Life threatening haemorrhage after anterior needle aspiration of pneumothoraces. A role for lateral needle aspiration in emergency decompression of spontaneous pneumothorax.

Needle aspiration is a recognised emergency treatment of spontaneous pneumothorax and in the case of suspected tension is usually performed before chest radiography. Three cases are described of apparent life threatening haemorrhage after anterior aspiration in the second intercostal space, mid-clavicular line (2ICS MCL) requiring resuscitation, and transfer to a cardiothoracic unit. In these patients there was no evidence of haemothorax on initial presentation. Lateral needle aspiration, in the site recommended for chest drain insertion, the 5th intercostal space, anterior axillary line (5ICS ALL) is technically easy and may be a potentially safer option for decompressing pneumothoraces.

Randomised trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection.

OBJECTIVES: To assess whether immediate post-operative enteral feeding in patients who have undergone gastrointestinal resection is safe and effective. DESIGN: Randomised trial of immediate post-operative enteral feeding through a nasojejunal tube v conventional postoperative intravenous fluids until the reintroduction of normal diet. SETTING: Teaching hospitals in London. SUBJECTS: 30 patients under the care of the participating consultant surgeon who were undergoing elective laparotomies with a view to gastrointestinal resection for quiescent, chronic gastrointestinal disease. Two patients did not proceed to resection. MAIN OUTCOME MEASURES: Nutritional state, nutritional intake and nitrogen balance, gut mucosal permeability measured by lactulose-mannitol differential sugar absorption test, complications, and outcome. RESULTS: Successful immediate enteral feeding was established in all 14 patients with a mean (SD) daily intake of 6.78 (1.57)MJ (1622 (375) kcal before reintroduction of oral diet compared with 1.58 (0.14) MJ (377 (34) kcal) for those on intravenous fluids (P < 0.0001). Urinary nitrogen balance on the first postoperative day was negative in those on intravenous fluids but positive in all 14 enterally fed patients (mean (SD) - 13.2 (11.6) g v 5.3 (2.7) g; P < 0.005). There was no difference by day 5. There was no change in gut mucosal permeability in the enterally fed group but a significant increase from the test ratios seen before the operation in those on intravenous fluids (0.11(0.06) v 0.15 (0.12); P < 0.005). There were also fewer postoperative complications in the enterally fed group (P < 0.005). CONCLUSIONS: Immediate postoperative enteral feeding in patients undergoing intestinal resection seems to be safe, prevents an increase in gut mucosal permeability, and produces a positive nitrogen balance.

Ischaemic preconditioning may abolish the protection afforded by ATP-sensitive potassium channel openers in isolated human atrial muscle.

The ATP-sensitive potassium channel (KATP channel) has been implicated in the mechanism underlying ischaemic preconditioning protection. This study based on human atrium compared the protective effects of ischaemic preconditioning with pre-operative nicorandil (a KATP channel opener with nitrate actions). We also examined the added effect of ischaemic preconditioning to that of nicorandil on ischaemic protection. The protective effects of other KATP channel openers devoid of nitrate actions were also examined. Atrial trabeculae harvested from patients undergoing routine myocardial revascularisation were divided on the basis of whether patients had been ingesting nicorandil orally preoperatively. Trabeculae were superfused with oxygenated Tyrode's solution and following stabilisation underwent 90 minutes simulated ischaemia followed by 120 minutes reoxygenation (n = 6 per group). Atrial trabeculae exposed to nicorandil underwent either no treatment (N), or ischaemic preconditioning (N + PC) using 3 minutes simulated ischaemia and 7 minutes reoxygenation prior to the 90 minutes simulated ischaemia. Similarly trabeculae not exposed to nicorandil underwent either no treatment, controls (C), or ischaemic preconditioning (PC). The experimental endpoint was recovery of contractile function presented as percentage baseline function. Further groups were examined using other KATP channels openers with and without ischaemic preconditioning. In the control group, following 120 minutes reoxygentation the recovery of function reached 28.8 +/- 3.5%. In contrast, exposure to nicorandil alone improved recovery of function (55.5% +/- 5.3) to a similar extent as PC (55.3% +/- 2.5) when compared to controls (p < 0.05, ANOVA). The addition of ischaemic preconditioning to nicorandil exposure abolished protection (29.7% +/- 3.1 ). Findings were confirmed using the other KATP channels openers. Clinically available nicorandil appears to afford ischaemic protection to isolated human atrial muscle. The addition of a short ischaemic episode to nicorandil exposure seems to completely abolish this protection. Although the mechanism underlying this effect remains unknown, we believe that this observation may have clinical implications.

TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family.

The DNA-binding factor TFEB contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region. This arrangement of interactive motifs has recently been observed in several other transcription factors and in the Myc family of oncogenes. TFEB was isolated by virtue of its binding to the major late promoter of adenovirus. DNA binding by a soluble protein was achieved by deleting a hydrophobic amino-terminal domain and permitted the structural analysis of the oligomerization and DNA-binding properties of TFEB. TFEB specifically bound DNA as both a homodimer and a heterodimer with another b-HLH-LZ protein TFE3. The LZ domain was essential for homo- or hetero-oligomerization and high-affinity DNA binding. In the absence of DNA a tetramer-sized form of TFEB was observed that dissociates to bind added DNA as a dimer. Binding by TFEB and TFE3 to related, but different, naturally occurring DNA target sequences was observed with distinct binding preferences. Analysis of basic domain residues in this family of proteins revealed a pattern of sequence conservation predictive of an interacting alpha-helical face. Common oligomerization and DNA-binding features suggest the b-HLH-LZ domain structure to define a distinct family of DNA-binding factors.

Comparison of the protective effects of a highly selective ATP-sensitive potassium channel opener and ischemic preconditioning in isolated human atrial muscle.

The ATP-sensitive K+ channel (K[ATP] channel) has been implicated in the mechanism of ischemic preconditioning. We compared the protective effects of ischemic preconditioning and a highly selective K(ATP) channel opener, BMS 180448, in human myocardium. BMS 180448 was either used alone or in combination with the K(ATP) channel blocker glibenclamide. Human atrial trabeculae derived from the right atrial appendage were suspended in an organ bath, superfused with oxygenated Tyrode's solution at 37degrees C, and paced at 1 Hz. Experimental groups (n = 6 in each) were as follows: (1) control (C)--90 minutes hypoxic substrate-free perfusion at 3 Hz (simulated ischemia), followed by 120 minutes of reoxygenation with substrate at 1 Hz (reperfusion); (2) preconditioning (PC)--3 minutes simulated ischemia, 7 minutes reperfusion, followed by 90 minutes simulated ischemia and 120 minutes reperfusion; (3) BMS 180448 (BMS)--exposure to the drug for 5 minutes prior to 90 minutes simulated ischemia and 120 minutes reperfusion; (4) BMS 180448 + glibenclamide (BMS + G)--glibenclamide exposure for 10 minutes, and BMS for 5 minutes prior to 90 minutes simulated ischemia and 120 minutes reperfusion. Force of contraction prior to the commencement of the protocol was assigned the arbitrary value of 100%. Percentage recovery of contractile function at 120 minutes reperfusion was used as the endpoint. BMS (59.2 +/- 8.6%) and preconditioning (50.5 +/- 3.6% ) produced a similar degree of recovery of function at the end of 120 minutes of reperfusion; this was significantly different from the untreated control group (20.8 +/- 3.5%, p < 0.05, ANOVA). When glibenclamide was added prior to BMS, protection was lost (20.5 +/- 2.7%). In this human atrial preparation, a highly selective K(ATP) channel opener mimicked the protective effect of ischemic preconditioning. This protective effect of BMS was abolished by glibenclamide. These findings confirm that the mechanism of ischemic preconditioning in human muscle may be mediated via opening of the K(ATP) channel.