Effects of a clinically detectable PDA on pulmonary mechanics measures in VLBW infants with RDS.

We examined the effect of a clinically detectable patent ductus arteriosus (PDA) and its successful treatment with indomethacin on serial measures of pulmonary mechanics in 10 very-low-birthweight (VLBW) intubated infants with respiratory distress syndrome (RDS). Pulmonary mechanics were measured by the passive expiratory flow technique. Total respiratory system compliance (Crs) gradually improved as RDS resolved. However, a significant decrease in mean Crs was associated with the development of a clinically detectable PDA, ranging from 1.51 +/- 0.21 to 0.90 +/- 0.08 mL/cmH2O/m (P less than 0.05). We also noted an increase in mean Crs, from 0.90 +/- 0.08 to 1.49 +/- 0.21 mL/cmH2O/m (P less than 0.05), after successful treatment of a PDA with indomethacin. Total respiratory system resistance (Rrs) did not change. We conclude that a clinically significant PDA is associated with a decreased Crs and that successful treatment of a PDA with indomethacin is associated with an improvement in lung compliance. These findings imply that the development of a clinically detectable PDA and its subsequent treatment complicates the interpretation of pulmonary mechanics data in VLBW infants with RDS.     

Initial treatment with fixed-dose combination rosiglitazone/glimepiride in patients with previously untreated type 2 diabetes

Aim: This study assessed the efficacy and safety of two different dosing regimens of fixed‐dose combination (FDC) rosiglitazone (RSG) plus glimepiride (GLIM) compared with RSG or GLIM monotherapy in drug‐naive subjects with type 2 diabetes mellitus (T2DM). Methods: Drug‐naive subjects (n = 901) were enrolled into this 28‐week, double‐blind, parallel‐group study if their glycosylated haemoglobin A_1c (HbA_1c) was >7.5% but ≤12%. Subjects were randomized to receive either GLIM [4 mg once daily (OD) maximal], RSG (8 mg OD maximal) or RSG/GLIM FDC regimen A (4 mg/4 mg OD maximal) or RSG/GLIM FDC regimen B (8 mg/4 mg OD maximal). Patients were assessed for efficacy and safety every 4 weeks for the first 12 weeks of the study, and at weeks 20 and 28. The primary efficacy endpoint was change in HbA_1c from baseline. Key secondary endpoints included the proportion of patients achieving recommended HbA_1c and fasting plasma glucose (FPG) targets; change from baseline in FPG, insulin, C‐reactive protein (CRP), adiponectin, free fatty acids and lipids; and percentage change in homeostasis model assessment‐estimated insulin sensitivity and β‐cell function. Safety evaluations included adverse‐event (AE) monitoring and clinical laboratory evaluations. Results: At week 28, both RSG/GLIM FDC regimens significantly reduced HbA_1c (mean ± s.d.: ?2.4 ± 1.4% FDC regimen A; ?2.5 ± 1.4% FDC regimen B) to a greater extent than RSG (?1.8 ± 1.5%) or GLIM (?1.7 ± 1.4%) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 vs. both RSG and GLIM). Significantly more subjects achieved HbA_1c target levels of ≤6.5 and <7% with either RSG/GLIM FDC regimen compared with RSG or GLIM alone (model‐adjusted odds ratio, p < 0.0001 for both comparisons). Similarly, a significantly greater reduction in FPG levels was observed in subjects treated with the RSG/GLIM FDC [mean ± s.d. (mg/dl): ?69.5 ± 57.5 FDC regimen A; ?79.9 ± 56.8 FDC regimen B) compared with RSG (?56.6 ± 58.1) or GLIM (?42.2 ± 66.1) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 for both comparisons). Improvement in CRP was also observed in subjects who were treated with a RSG/GLIM FDC or RSG monotherapy compared with GLIM monotherapy. RSG/GLIM FDC was generally well tolerated, with no new safety or tolerability issues identified from its monotherapy components, and a similar AE profile was observed across FDC regimens. The most commonly reported AE was hypoglycaemia, and the incidence of confirmed symptomatic hypoglycaemia (3.6–5.5%) was comparable among subjects treated with an RSG/GLIM FDC and GLIM monotherapy. Conclusions: Compared with RSG or GLIM monotherapy, the RSG/GLIM FDC improved glycaemic control with no significant increased risk of hypoglycaemia. RSG/GLIM FDC provides an effective and well‐tolerated treatment option for drug‐naive individuals with T2DM.     

Intestinal helminth infestation is associated with increased bronchial responsiveness in children

Non-atopic asthma is the predominant phenotype in non-affluent parts of Latin America. We recently reported that infestation with Ascaris lumbricoides increased the risk of non-atopic asthma in less affluent areas of Brazil but the mechanism is unclear. The present study was conducted to determine whether helminth infestation is associated with heightened bronchial responsiveness (BHR), a common finding in asthma. A random sample of 50 asthmatic and 50 non-asthmatic controls (mean age 10.1 years) were selected from a larger cohort (n = 1,011) without knowledge of their helminth infestation status. Three stool samples were collected from each child on different days and each sample was analyzed by the Kato-Katz method for quantitative determination of helminth eggs. Bronchial provocation tests were performed with inhaled 4.5% hypertonic saline using the ISAAC Phase II standardized protocol. There was no difference between the prevalence of positive BHR in the asthmatics (20.4%) compared with the controls (14.6%) (P = 1.0). Helminth infestation was detected in 24.0% of children, with A. lumbricoides being the most common. Children with high load infestation (>or=100 eggs/g) were five times more likely to have BHR than children with low load or no infestation. Despite the small sample size the results of the present study suggest that the link between high load helminth infestation and non-atopic asthma may be mediated via heightened bronchial responsiveness, possibly due to an inflammatory response to the pulmonary phase of the helminth life cycle.     

Effects of noradrenaline and isoproterenol on cardiopulmonary function in a canine model of acute pulmonary hypertension

The authors investigated acute cardiopulmonary effects of noradrenaline and isoproterenol infusion in a canine model of increased pulmonary vascular resistance (PVR) and decreased cardiac output (CO). In six anesthetized, ventilated dogs, autologous blood clots were injected over approximately two hours to increase right ventricular (RV) afterload and decrease CO. After CO had decreased 40 percent dogs were treated with noradrenaline or isoproterenol in alternate sequence. Both drugs increased stroke volume but only isoproterenol affected CO. Flow increased from 1.3 to 3.0 L X min-1 (p less than .01) with isoproterenol infusion. Corresponding to the increase in CO, RV filling pressure and PVR decreased, from 9 to 5 mm Hg, and from 36 to 16 mm Hg X L-1 X min (p less than .01) respectively. When a moderate decrease in CO complicates an acute increase in PVR, isoproterenol may be an excellent drug to treat the decrease in flow.     

The effect of an educational program upon hospital antibiotic use

The effect of an educational program on the use of antibiotics was studied in a university-affiliated Veterans Administration Hospital. Following an initial survey of antibiotic usage, educational presentations of the collected data were made to the hospital staff which included specific prescribing errors and alternative recommendations. Then, another survey was conducted. Measurable changes following the educational presentations were limited to decreasing costs of unjustified antibiotic use. An effect was noted in decreasing unjustified use of antibiotics in prophylactic situations, but this remained the most common misuse. Thus, an educational program directed at specific prescribing errors produced little noticeable effect on the use of antibiotics in a university-affiliated hospital. The study indicates that more direct measures, such as control of use of particular antibiotics, may be required to produce a meaningful change in prescribing practices.     

Embolisation procedures in congenital heart disease.

Eight therapeutic embolisation procedures were performed by the transcutaneous catheter technique in seven patients with congenital heart disease. After surgical correction of tetralogy of Fallot (four patients), catheter embolisation was used to occlude two large aortopulmonary collaterals (one patient), three small aortopulmonary collaterals (one patient), and two Blalock-Taussig shunts (two patients). In two patients congenital coronary anomalies were occluded--a coronary arteriovenous malformation and a coronary artery/bronchial artery anastomosis. In one patient a pulmonary arteriovenous malformation was embolised. Detachable balloons were used to occlude six large arteries, the three small arteries were occluded with small gelfoam fragments, and the pulmonary arteriovenous malformation was occluded with multiple steel coils and large gelfoam pieces. Successful occlusion was achieved in all cases. No complications were encountered and the procedure was well tolerated even in the two patients receiving postoperative intensive care. Therapeutic embolisation in suitable cases is a safe and effective alternative to surgery and the detachable balloon technique is effective in occluding high flow vessels.     

Determination of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in serum and plasma: comparisons using the Bland–Altman method

The measurement of circulating insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) have significant implications in the risk assessment of various diseases (e.g. cancer) and growth abnormalities. It is often assumed that values measured in serum and plasma are interchangeable. This study challenges this assumption by comparing determinants using the Bland-Altman method. Blood was obtained from 47 healthy volunteers (age 21-72 years) in serum, heparin plasma and EDTA plasma, and IGF-I, IGF-II, IGFBP-2, and IGFBP-3 measured, and results compared. Mean values for IGF-I, IGF-II, IGFBP-2 and IGFBP-3 determined in all three media were generally comparable; correlations were generally strong and significant (P<0.001). However, the Bland-Altman plots revealed significant lack of agreement for many analytes measured in EDTA plasma compared with serum and heparin plasma. Additionally, the ranges of the limits of agreement were consistently greater for EDTA plasma compared with the other two methods. These findings emphasize the need to standardize methods of collecting blood samples in future epidemiological studies and trials.     

A single ovary of Anolis carolinensis responds more to exogenous gonadotropin if the contralateral ovary is absent.

The lizard Anolis carolinensis exhibits asymmetric ovarian growth. At any given time, the larger ovary (LO) contains a larger follicle than does the smaller ovary (SO). Physiologically hypophysectomized females with quiescent ovaries were treated with gonadotropin (ovine FSH) or saline vehicle after either surgical removal of the LO or sham operation. The smaller ovaries of initial control, sham-operated, and hemiovariectomized (HO) females were similar in weight and follicular size. Therefore, endogenous gonadotropin secretion remained at subthreshold levels during the experiment and after HO. FSH significantly stimulated ovarian follicular growth in both sham-operated and HO females. However, the response of the SO of HO females to FSH was significantly greater than that in sham-operated females. These results demonstrate a greater sensitivity of the SO to FSH if the LO is absent.     

Enteric and central contributions to intestinal dysmotility in irritable bowel syndrome

The aim of the study was to further elucidate the pathophysiology of irritable bowel syndrome and its subgroups by examining and comparing alterations in small bowel motility, specifically phase II and phase III components of the migrating motor complex. Prolonged recordings of interdigestive small bowel motility were obtained during both diurnal and nocturnal periods in 20 patients with irritable bowel syndrome--10 with predominant constipation and 10 with predominant diarrhea--and in 10 healthy subjects. Diurnal amplitude (mean +/- SD) of phase III activity fronts was lower (P less than 0.05) in constipation-predominant patients (16.3 +/- 3.1 mm Hg) than in diarrhea-predominant patients (20.2 +/- 3.1) or controls (20.9 +/- 2.7). Similar findings were observed nocturnally. Phase III cycle length was also significantly prolonged diurnally in constipation-predominant patients when compared to the other groups. In the diarrhea-predominant group repetitive and rapidly propagated bursts of contractions were observed in eight patients, and this pattern occupied a significantly greater proportion of phase II motor activity than in controls. These alterations in phase II and in phase III components of the migrating motor complex suggest that both local (enteric) and more central mechanisms may operate to produce intestinal dysmotility in the irritable bowel syndrome and that these mechanisms differ according to the predominant alteration of bowel habit.