Catheter balloon-related urethral trauma in children

Aim:   To review urethral injuries arising from incorrect balloon inflation in children undergoing urinary catheterisation.
Method:   Retrospective review from 1995–2006. Children who sustained catheter-related injury at The Children's Hospital at Westmead were identified through medical records database and reviewed.
Results:   Six patients were identified over the 11-year period. All six were boys. Age ranged from <1 month to 16 years. All but one occurred in hospital. All injuries were confirmed by urethrogram. Bulbar and prostatic urethra was involved in an equal number of children studied. Three patients required suprapubic catheters. Follow-up imaging revealed healing without stricture in all patients.
Conclusion:   Balloon-related urethral trauma can be avoided by educating health-care professionals on proper placement and confirmation of position of catheter. Though there were no long-term complications noted, a temporary suprapubic diversion may be needed.     

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT).Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT.Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m² vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin.FundingNational Institute for Health Research.     

Respiratory distress syndrome treated with human surfactant: radiographic findings

Chest radiographs of 18 newborns treated with endotracheal instillation of human surfactant for respiratory distress syndrome (RDS) were compared with those of 18 similar but untreated infants. In the treated infants, severity of RDS significantly improved after surfactant administration. Most treated infants (16/18) exhibited a left-to-right shunt, presumably through a patent ductus arteriosus; similar findings were noted in untreated infants (17/18). Complications of respiratory assistance in the treated infants included transient pulmonary interstitial emphysema (n = 1), pneumothorax (n = 1), and mild (n = 4) to moderate (n = 2) bronchopulmonary dysplasia; the incidences of these complications did not exceed those in untreated infants. In three treated infants, a transient interstitial lung disease developed 3-4 days after surfactant administration.     

Catabolism of human tissue plasminogen activator in mice

The catabolism of human tissue plasminogen activator (t-PA) was studied in mice. The clearance of t-PA labeled with iodine 125 was rapid (t1/2). The clearance of phenylmethylsulfonyl-125I-t-PA, which is active site-inhibited, was identical to the active enzyme. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the vast majority of 125I-t-PA injected into the circulation was present as free enzyme and not in a complex with inhibitors. The clearance of 125I-t-PA was unaltered by large molar excesses of several ligands of known clearance specificities, including macroalbumin, asialoorosomucoid, and diisopropylphosphorylthrombin and was also not altered in the presence of a 1,000-fold molar excess of unlabeled t-PA. Organ distribution studies demonstrated that the early rapid clearance of 125I-t-PA occurred in hepatocytes, followed by a later renal phase of clearance. The clearance of 125I-urokinase (UK) also was studied and was very similar in all aspects to the clearance of 125I-t-PA. These results suggest that both t-PA and UK are cleared from the circulation by unique nonsaturable processes localized in the liver that are independent of the proteinase active site.     

The SV stent study: a prospective, multicentre, angiographic evaluation of the BiodivYsio phosphorylcholine coated small vessel stent in small coronary vessels

OBJECTIVE: To evaluate the use of the phosphorylcholine (PC) coated BiodivYsio small vessel (SV) stent in native coronary vessels of small calibre. DESIGN AND SETTING: Prospective, multi-centre, multi-national registry with 6-month clinical and core-lab angiographic follow-up. Adverse events were adjudicated by a Clinical Events Committee (CEC) and included peri-procedural analysis of cardiac enzymes. PATIENTS: Patients with signs or symptoms of ischaemia with an identified target lesion in an epicardial vessel with reference diameter 2.0-2.75 mm were enrolled. Intervention in other epicardial territories in the same patient was permitted. RESULTS: Recruitment of 150 consecutive lesions (in 143 patients) was completed in 19 centres in Europe and Israel. The stent was deployed successfully in all but one lesion. At 6 months, 1 patient (1%) had experienced sudden cardiac death, 4 further patients (3%) had a non-Q wave MI, and a further 24 patients (17%) had repeat revascularisation of a study target vessel. The mean reference vessel diameter prior to stenting was 2.2 mm (S.D. 0.4). Mean minimal luminal diameters at pre-procedure, post procedure and follow-up were 0.6 mm (S.D. 0.3), 2.0 mm (S.D. 0.4) and 1.2 mm (S.D. 0.6), respectively. The late lumen loss index was 0.55 (S.D. 0.53) with a binary restenosis rate of 32%. CONCLUSIONS: In stenting of selected lesions in small vessels, the BiodivYsio SV stent demonstrated high rates of implant success. The rates of major adverse cardiac events (MACE), angiographic restenosis and repeat revascularisation are similar to those reported in other small vessel bare metal stent studies.     

Preparation of polyethylene glycol-tissue plasminogen activator adducts that retain functional activity: characteristics and behavior in three animal species

Conditions were defined for the derivatization of recombinant tissue plasminogen activator (rt-PA) with polyethylene glycol (PEG) so as to retain functional activity as a possible means of producing a t-PA species with a prolonged circulating lifetime. Derivatives with a wide range of retention of activities were prepared by varying the concentration and species of activated PEG. The specific activities of the PEG-rt-PA derivatives were dependent on the method of assay. Assays using preformed fibrin gave higher estimates of retention of activity than assays using soluble components. Plasma elimination studies in mice and rats indicated prolonged circulating lifetimes for the radiolabeled PEG-rt-PA derivatives after a rapid clearance and distribution phase; however, the disappearance of functional activity was much more rapid than the disappearance of radiolabeled material. The PEG-rt-PA derivatives appeared to accumulate in tissues above their interstitial fluid concentrations and were rapidly inactivated, apparently by reaction with the plasma protease inhibitors. These results were consistent with the inactivation of the PEG-rt-PA derivatives in rat plasma in vitro. A somewhat longer half-life (t1/2) of the one derivative studied was observed in dogs (t1/2, 16 minutes) as compared with the rat (t1/2, five minutes). This was sufficient to confer thrombolytic activity upon the derivative (administered by bolus injection) in contrast to native rt-PA. The potential of PEG-modified rt-PA as a long-lived thrombolytic agent in humans will depend, however, on whether there will be a further extension of the t1/2 because of a reduction in clearance and/or a reduction in the rate of inactivation.     

The role of endothelium in factor Xa regulation: the effect of plasma proteinase inhibitors and hirudin

The role of endothelium in the inhibition of human factor Xa was studied in a plasma environment. Human factor Xa can bind to and function on bovine aortic endothelium in a manner similar to that of bovine factor Xa. Approximately 70% of the bound factor Xa is subject to inhibition by plasma proteinase inhibitors, and the remaining 30% is irreversibly bound as part of a 125 Kd membrane-associated complex not subject to proteolytic degradation. The proportion reversibly bound and its rate of release do not alter with changes in calcium, citrate, heparin, or active proteinase inhibitor concentrations. The principal plasma proteinase inhibitor of human factor Xa was antithrombin III, which accounted for 60% to 65% of factor Xa released from endothelium, with alpha 1-proteinase inhibitor inactivating 20% to 25% and alpha 2- macroglobulin approximately 15%. All of the reversibly bound factor Xa was identified in complex with one of these three proteinase inhibitors. The thrombin active-site inhibitor hirudin was found to markedly accelerate the displacement of reversibly bound factor Xa from the endothelium and to associate specifically with factor Xa without a loss of activity toward chromogenic substrates, perhaps accounting for a novel mechanism of anticoagulation.     

Electron microscopic localization of factor-VIII-related antigen in adult human blood vessels

We have localized factor-VIII-related antigen, using immunofluorescence and electron microscopy, in adult human blood vessels. In addition to its presence in endothelial cells, the antigen was localized within subendothelium and the layers of elastic lamina closest to the lumen. Also, we provide the first morphological evidence that factor-VIII- related antigen is associated with collagen fibrils within the vessel wall. These studies suggest that this subendothelial factor-VIII- related antigen may play a role in the adhesion of platelets to subendothelial components following endothelial injury.