The effect of an education programme (MEDIAS 2 BSC) of non-intensive insulin treatment regimens for people with Type 2 diabetes: a randomized, multi-centre trial.

AIMS: A self-management oriented education programme (MEDIAS 2 BSC) for people with Type 2 diabetes who are on a non-intensive insulin treatment regimen was developed. In a randomized, multi-centre trial, the effect of MEDIAS 2 BSC was compared with an established education programme that acted as a control group. METHODS: The primary outcome was the impact of MEDIAS 2 BSC on glycaemic control. Secondary outcomes included the incidence of severe hypoglycaemia, hypoglycaemia unawareness, diabetes-related distress, diabetes knowledge, quality of life and self-care behaviour. RESULTS: In total, 182 participants were randomized to the control group or MEDIAS 2 BSC [median age 64.0 (interquartile range 58.0-68.5) vs. 63.5 (57.0-70.0) years; HbA1c 62.8 ± 12.7 mmol/mol vs. 63.7 ± 14.0 mmol/mol; 7.9% ± 1.2% vs. 8.0% ± 1.3%]. After a 6-month follow-up, there was a mean decrease in HbA1c of 3.5 mmol/mol (0.32%) in the control group and 6.7 mmol/mol (0.61%) in MEDIAS 2 BSC. After adjusting for baseline differences and study centre, the mean difference between the groups was -3.3 mmol/mol [95% confidence interval (CI) -0.54 to -5.90 mmol/mol] [-0.30% (95% CI -0.05 to -0.54)] in favour of MEDIAS 2 BSC (P = 0.018). There were no increases in severe hypoglycaemia or hypoglycaemia unawareness. The education programmes had no significant effects on psychosocial outcome variables. CONCLUSION: MEDIAS 2 BSC was more effective in lowering HbA1c than the control condition. MEDIAS 2 BSC is a safe educational tool that improves glycaemic control without increasing the risk for hypoglycaemia. (Clinical Trials Registry No; NCT 02748239).

Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus.

The population pharmacokinetics of intravenous indomethacin were investigated with 665 indomethacin serum concentrations from 83 neonates (mean +/- SD: gestational age, 28.8 +/- 2.5 weeks; postnatal age, 5.7 +/- 4.7 days; birth weight, 1.13 +/- 0.40 kg) receiving indomethacin for symptomatic patent ductus arteriosus. A one-compartment open model was used for pharmacokinetic analysis. Hypotheses were tested to determine which developmental and demographic data influenced clearance (CL) and volume of distribution (V(area)). In the final regression equation CL and V(area) were modeled as a function of body weight and postnatal age (PNA) from 0 to 20 days. Final estimates were as follows: CL (ml/hr) = 2.63.weight (kg) + 0.244.PNA (days) and V(area) (L) = 0.28.weight (kg) + 0.0041.PNA (days). The coefficients of variation for interindividual variability in CL and V(area) were 77% and 28%, respectively. Intraindividual variability was 19%. These mean population parameter estimates should prove useful in designing dosage regimens to achieve desired indomethacin concentrations for neonates from 0 to 20 days of age with symptomatic patent ductus arteriosus.

Prolonged electrical systole and QT greater than QS2 secondary to coronary artery disease.

Dyssynchronous depolarization-repolarization in the left ventricular (LV) myocardium may produce QT greater than QS2 or long QT. In 41 patients with coronary artery disease (CAD) and LV aneurysm, 46 patients with CAD and a history of acute myocardial infarction (AMI) but no LV aneurysm, and 52 patients with CAD without previous AMI, QT and QS2 were measured simultaneously at a speed of 100 mm/s within 48 hours of cardiac catheterization. Patients receiving class I antiarrhythmic drugs were excluded. The incidence of QT greater than QS2 was significantly greater in patients with LV aneurysm (71%) than in those with previous AMI (22%) and those with CAD but no previous AMI (20%) (p less than 0.001). Likewise, the incidence of long QT corrected for heart rate was significantly greater in patients with LV aneurysm (54%) than in those with previous AMI (7%) and those with CAD and no previous AMI (6%) (p less than 0.0001). The incidence of QT greater than QS2 in another 19 patients with previous AMI who were receiving digitalis therapy was significantly greater (65%) than in those with previous AMI but not receiving digitalis therapy (22%) (p less than 0.001). The incidence of long QT corrected for heart rate and QT greater than QS2 was not statistically different between patients with previous AMI and those with CAD but no previous AMI. The QT greater than QS2 or long QT in patients with aneurysm is probably a result of dyssynchronous depolarization or repolarization within or in the border zone of the LV aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Electro-oculogram testing in fundus flavimaculatus.

Electro-oculogram (EOG) measurements were obtained on seven patients with moderately extensive lesions of fundus flavimaculatus. Each patient was tested by two different methods of measuring EOG light-peak to dark-trough ratios. The results show that erroneously low ratios can be observed unless a diffusing sphere is employed in the determination of light-peak to dark-trough ratios in fundus flavimaculatus and presumably other diseases that affect primarily the posterior pole.

Premature closure of the foramen ovale and hypoplasia of the left heart.

Although premature closure of the foramen ovale has been proposed as a possible cause of hypoplastic left heart syndrome, very few such cases have been described. We have seen two examples of the combination and no associated malformations. In both the foramen was firmly closed on its left atrial aspect and the dimensions of the left sided structures were well below normal values.

Indomethacin for patent ductus arteriosus closure. Application of serum concentrations and pharmacodynamics to improve response.

Indomethacin dosing for patent ductus arteriosus closure has been standardized despite wide interpatient variability in indomethacin pharmacokinetics. We compared a novel indomethacin dosing approach using individual pharmacokinetic and pharmacodynamic information (group A) with a control group from our institution (group B) and a level 3 university-based intensive care nursery (group C) who were dosed using current dosing guidelines. Permanent patent ductus arteriosus closure was achieved in 27 of 28 (96.4%) group A patients, 10 of 16 (62.5%) group B patients, and 7 of 13 (52.8%) group C patients. Success rates were significantly higher in group A than Groups B and C (P less than .02). Renal toxicity was the only toxicity reported in any group. The major manifestations of renal toxicity, ie, urine output below 1 mL/kg/h or increased serum creatinine by greater than or equal to 0.5 mg/dL, occurred in none of the group A patients but in seven (43.8%) group B and eight (61.5%) group C patients. Renal toxicity was significantly greater in groups B and C than group A (P less than .02). A pharmacodynamic concentration versus response curve was developed and proved predictive of patent ductus arteriosus closure rates in previous studies where indomethacin concentration versus response data were available. Serum concentration monitoring is a valuable adjunct to indomethacin therapy for patent ductus arteriosus closure, especially when a pharmacodynamic approach is used.

Endocardial fibroelastosis with coronary artery thromboembolus and myocardial infarction.

We report a case of an 18-month-old male, born to a woman with third trimester febrile illness, who had a history of congestive heart failure and respiratory distress, cardiomegaly, and electrocardiographic (ECG) findings suggestive of cardiomyopathy and myocarditis. After gradual improvement in heart size and function with pharmacologic therapy, he developed a terminal episode of respiratory distress and cardiogenic shock, with ECG findings of an anterolateral infarct. At autopsy it was found that endocardial fibroelastosis with mural thrombi in the left ventricle had been complicated by thromboembolism to the left anterior descending coronary artery, resulting in transmural infarction of the anteroseptal region of the left ventricle. Myocardial infarction is a potential but unusual thromboembolic complication of endocardial fibroelastosis. A high index of suspicion for coronary artery thromboemboli should be maintained in pediatric patients with cardiomyopathy and suspected myocardial infarction.

Right ventricular aneurysm due to ischemic disease. Diagnosis by radionuclide angiography with localization of the site of PVC origin by phase analysis.

A case of right ventricular aneurysm due to coronary artery disease in a 69-year-old male with no prior history of surgery or chest trauma is reported. The presence of the aneurysm was diagnosed by gated radionuclide angiography and confirmed by contrast angiography. This is the first description of an isolated right ventricular aneurysm on the basis of ischemic disease. In addition, the patient had recurrent ventricular tachycardia and frequent premature ventricular contractions (PVC's). Using radionuclide angiographic phase analysis of the PVC's, their apparent origin was localized to the margin of the right ventricular aneurysm.

Haemodynamic, electrocardiographic, electrophysiologic and pharmacokinetic activity of 4'-hydroxypropranolol in dogs.

We determined the haemodynamic, electrocardiographic and electrophysiologic effects, and the pharmacokinetic properties of 4'-hydroxypropranolol (4'-OHP) by conducting three different experiments in dogs. In experiment 1 the plasma concentrations of 4'-OHP (mg/kg, i.v.) in pentobarbital anaesthetized dogs were determined by HPLC and pharmacokinetic parameter values were estimated. The terminal elimination half-life (t1/2) for 4'-OHP was 69.4 min, the apparent volume of distribution (Vd) was 3.39 L/kg and the total clearance (Clt) was 53.6 mL/min.kg. These data were subsequently used to calculate the loading and maintenance doses of 4'-OHP required to produce targeted steady-state plasma concentrations for 4'-OHP of 30, 60, 120, 240 and 480 ng/mL. In experiment 2 the haemodynamic and electrocardiographic effects for target plasma concentrations of 4'-OHP were determined in two groups of pentobarbital anaesthetized dogs, and beta-blocking activity was assessed by infusion or bolus doses of isoproterenol. The haemodynamic and electrocardiographic effects of the target plasma concentrations (30, 60, 120 ng/mL) of 4'-OHP were first determined in seven pentobarbital anaesthetized dogs (Group 1). Beta blocking activity was assessed by the infusion of 0.1 microgram/kg/min isoproterenol. The infusion of 4'-OHP produced dose dependent decreases in heart rate, cardiac output, dP/dtmax, mean arterial pressure and left ventricular diastolic pressure. The PR interval of the lead II electrocardiogram increased and the QTc interval decreased. These haemodynamic and electrocardiographic changes became apparent at plasma 4'-OHP concentrations equal to or greater than 30 ng/mL. Plasma concentrations of 4'-OHP equal to or greater than 30 ng/mL prevented the haemodynamic and electrocardiographic effects of isoproterenol infusion. In group 2 dogs, (seven dogs) the haemodynamic and electrocardiographic effects of target plasma concentrations (30, 60, 120, 240, 480 ng/mL) of 4'-OHP were evaluated and beta-blocking activity was assessed by the i.v. bolus administration of 1 and 4 micrograms/kg of isoproterenol. The infusion of 4'-OHP produced haemodynamic and electrocardiographic changes similar to those in group 1 dogs. In addition, the QRS duration of the electrocardiogram increased at plasma concentrations of 4'-OHP equal to or greater than 240 ng/ mL. The haemodynamic and electrocardiographic effects of i.v. bolus dose administrations of 1 and 4 micrograms/kg isoproterenol were abolished by plasma concentrations of 4'-OHP equal to or greater than 240 ng/mL. In experiment 3 we determined the electrophysiologic effects of 10(-9) to 10(-5) mmol/L 4'-OHP on Tyrodes superfused bundles of canine Purkinje fibres. Action potential duration and the effective refractory period decreased at superfusate concentrations of 4'-OHP equal to or greater than 10(-7) mmol/L. Action potential overshoot, action potential total amplitude, the rate of rise of phase 0 (dV/dt) and spontaneous rate decreased at superfusage concentrations of 4'-OHP equal to or greater than 800 ng/mL. These studies demonstrate that: 1) 4'-OHP produces haemodynamic. electrocardiographic and electrophysiologic effects similar to those of other beta-blocking drugs in pentobarbital anaesthetized dogs; 2) the haemodynamic and electrocardiographic effects produced by 4'-OHP are apparent at relatively low plasma concentrations (30 ng/mL); 3) the concentrations of 4'-OHP that are required to produce direct cardiac electrophysiologic effects are unlikely to be responsible for clinical antiarrhythmic activity and 4) 4'-OHP blocks the haemodynamic and electrocardiographic effects of infusions and i.v. bolus administration of isoproterenol.

Cerebral arteriovenous malformation presenting as persistent fetal circulation. Diagnosis by cross-sectional echo.

Two infants with cerebral arteriovenous malformation (CAVM), both initially seen with persistent fetal circulation, were studied with cross-sectional echo. The descending aorta, which is dilated in infants with CAVM, was identified in the subxiphoid four-chamber and short-axis views in both infants. In both infants the arteriovenous malformation was readily identified by cross-sectional echo as a lucency within the brain. Pulsation of the cranial lucency was noted in one infant, but only still frames from the head echo were preserved in the other infant, and pulsation was not commented on in that case.

Selective cyanosis of the right arm. Isolation of right subclavian artery from aorta with bilateral ductus arteriosus and pulmonary hypertension.

A sixteen-month-old child presented with cyanosis of the right arm. Investigation revealed bilateral persistent ductus arteriosus with isolation of the right subclavian artery from the aorta. Pulmonary vascular resistance and pulmonary arterial pressure were elevated so that the right subclavian artery received desaturated blood from the right pulmonary artery via the persistent right ductus arteriosus.

Echocardiographic and hemodynamic relationships of ejection sounds.

The physiologic correlates of ejection sounds have been studied by simultaneous phonocardiograms, echocardiograms and high fidelity pressure tracings. Ejection sounds associated with semilunar valve stenosis or hypertension of the systemic or pulmonary circulation occur at the moment of complete opening of the aortic or pulmonary valve recorded echocardiographically. The start of opening of these valves occurs at the onset of the pressure rise in the corresponding great vessel and completion of valve opening always occurs on the pressure upstroke. The ejection sound in the presence of stenotic valves occurs with checking of the opening motion of the thickened valve cusps. Although the hypertensive ejection sounds also occur at the precise moment of full opening of the valve it remains to be seen whether this relationship is causal or coincidental.

A PC-based ultrasonic data acquisition system for computer-aided prosthetic socket design.

A PC-based ultrasound data acquisition system has been developed which uses compound scanning techniques to image a residual limb in a water tank. From the received ultrasonic eco data, the system produces cross-sectional images and reconstructs a three-dimensional (3-D) model of the limb. A commercial software for computer-aided prosthetic socket design was modified so that it can display both the external shape and cross-sectional image of the limb and allow the prosthetist to perform socket design with the help of a visualization of the limb's internal structure. The image resolution and measurement accuracy of the system were tested using a wire phantom and a contrast tissue mimicking phantom, respectively. Preliminary results from amputee patients are presented and the sources of measurement error are discussed.

Indomethacin pharmacokinetics in neonates: the value of volume of distribution as a marker of permanent patent ductus arteriosus closure.

Indomethacin (INDO) pharmacokinetics were examined in 18 neonates on 19 occasions, before and after patent ductus arteriosus (PDA) closure. Patients received INDO as an initial dose of 0.25 mg/kg intravenously, and INDO serum concentrations were measured 2 and 8 h after the dose. Subsequent doses were individualized based on clinical response, toxicity, and INDO pharmacokinetics. PDA status was confirmed echocardiographically at the start and end of therapy. INDO pharmacokinetic parameters varied from dose-to-dose within the same patient, and wide interpatient variability was also observed. Pre- and post-PDA closure, only INDO volume of distribution differed significantly (p less than 0.001) with mean values of 0.36 (+/- 0.06) L/kg and 0.26 (+/- 0.08) L/kg. The reason for this occurrence remains unclear. However, a new application for pharmacokinetics as a probe of physiology is demonstrated.

Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.

OBJECTIVES: To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus. DESIGN: Cohort study of neonates treated with gentamicin, according to a standard dosing protocol. SETTING: A 24-bed, Level III, neonatal intensive care unit. PATIENTS: Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age. INTERVENTIONS: All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model. MEASUREMENTS AND MAIN RESULTS: A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus. CONCLUSIONS: Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.