Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Neuropsychiatric Assessmenit of Children with Autism: A Population-Based Study

Thirty-five children with autistic disorder and 17 with autistic-like conditions underwent an exhaustive neurobiological evaluation, and the findings were contrasted with those obtained from various comparison groups. Almost 90 per cent of the children with autistic disorder and autistic-like conditions had major indications of brain damage or dysfunction. Some of those who did not show such abnormalities had a first-degree relative with Asperger syndrome. The rate of abnormality was similar to that of severely mentally retarded children, but in excess of that of normal children. Within the autism group, abnormality rate did not correlate with degree of mental retardation. It is concluded that autism has multiple biological aetiologies and that autistic symptoms in a child should always prompt a thorough medical/neurobiological evaluation.     

The influence of stimulus size on measured visual field extent in infants.

PURPOSE: To compare measured visual field extent for a 6 degrees stimulus (typical size used in studies of infants) with a 1.5 degrees stimulus (similar to the largest size used in Goldmann perimetry) in young infants. METHODS: A total of 120 infants (60 each at 3.5 months and 7 months of age) and 24 adults were tested monocularly with a kinetic perimetry procedure using a black double-arc perimeter. Each subject was tested with either a 6 degrees or 1.5 degrees white sphere, which was mounted on a black wand and moved smoothly toward the intersection of the perimeter arms at 3.4 degrees /s. Visual field extent along each perimeter arm was defined as the median of 2 to 3 measurements of the position of the leading edge of the stimulus when the subject made an eye movement toward the stimulus. RESULTS: The 6 degrees stimulus produced larger measured visual field extent than the 1.5 degrees stimulus in 3.5-month olds (temporal field only) and in 7-month olds (nasal and temporal field), but not in adults. CONCLUSIONS: Using the testing conditions of the present study, increasing stimulus size beyond the largest used in a Goldmann perimeter (approximately 2 degrees) increases measured visual field extent in young infants, but not in adults. This may relate to differences in peripheral summation areas or to differences in attentional factors between infants and adults.     

Association of Hypoalbuminemia on the First Postoperative Day and Complications Following Esophagectomy

Objective Changes in serum albumin may reflect systemic immunoinflammation and hypermetabolism in response to insults such as trauma and sepsis. Esophagectomy is associated with a major metabolic stress, and the aim of this study was to determine if the absolute albumin level on the first postoperative day was of value in predicting in-hospital complications. Methods A retrospective study of 200 patients undergoing esophagectomy for malignant disease at St. James Hospital between 1999 and 2005 was performed. Patients who had pre and postoperative (days 1, 3, and 7) serum albumin levels measured were included in the study. Patients were subdivided into three postoperative albumin categories <20 g/l, 20–25 g/l, >25 g/l. Logistic regression analysis was performed to calculate the odds of morbidity and mortality according to the day 1 albumin level. Results Patients with an albumin of less than 20 g/l on the first postoperative day were twice as likely to develop postoperative complications than those with an albumin of greater than 20 g/l (54 vs 28% respectively, p < 0.011). Correspondingly, these patients also had a significantly higher rate of Adult Respiratory Distress Syndrome (22 vs 5%, p < 0.001), respiratory failure (27 vs 8%, p < 0.01) and in-hospital mortality (27 vs 6% (p < 0.001). On multivariate logistic regression analysis, day 1 albumin level was independently related to postoperative complications (odds ratios, 0.89: 95%; confidence intervals, 0.83–0.96; p < 0.005). In addition, albumin <20 g/l on the first postoperative day was associated with the need for further surgery and a return to ICU. Conclusion Serum albumin concentration on the first postoperative day is a better predictor of surgical outcome than many other preoperative risk factors. It is a low cost test that may be used as a prognostic tool to detect the risk of adverse surgical outcomes.     

Effects of some non-steroidal anti-inflammatory drug copper complexes on polymorphonuclear leukocyte oxidative metabolism

Interaction between anti-inflammatory drugs and reactive oxygen metabolites must be considered in the course of pharmacological studies intended to develop new compounds. Effects of indomethacin, aspirin, and 3,5-diisopropylsalicylic acid (3,5-DIPS) and their copper complexes on PMNL oxidative metabolism and the evolution of an acute inflammatory reaction were studied in the rat. Experiments were performed in vitro by assessment of superoxide generation and reduction of chemiluminescence by PMNLs incubated or not (control) in medium containing various concentrations of these compounds. A dose-related decrease of these parameters was observed, however, copper complexes were found to be more effective than their parent drugs or Cu gluconate. Copper complexes were also more effective anti-inflammatory agents than their parent ligands or Cu gluconate when the volume of exudate and number of exudate PMNLs were assessed after induction of pleurisy in rats by injection of isologous serum. It is concluded that modulation of the PMNL oxidative burst by copper complexes offers an accounting for the anti-inflammatory activity of these compounds.     

A Pharmacoeconomic Model to Evaluate Antibiotic Costs

Study Objectives . To characterize patient sociodemographics and health, describe vancomycin treatment parameters and clinician-rated outcomes, and determine costs associated with treatment including preparation and administration, adverse events, and toxicity. Design . A prospective study to develop a model for costs associated with antibiotic treatment (vancomycin). Setting . A community hospital. Patients . One hundred adults with active infections. Interventions . Mean duration of therapy was 10 days, and most patients received 2000 mg/day. Serum concentrations were monitored in two of three patients. Detailed cost analyses were completed on a subset of 26 patients selected at random from the overall sample. Measurements and Main Results . Sepsis and skin and skin structure infections were the most common indications for vancomycin therapy. Treatment was effective in 81 patients, failed in 9, and was not evaluable in 10. Thirty-eight percent of patients experienced adverse events attributable to the drug. Phlebitis was common, and red man syndrome, nephrotoxicity, and ototoxicity were infrequent. Conclusions . Total cost of vancomycin treatment for 100 patients was $30,251: $23,855 for preparation and administration, $1710 for monitoring serum concentrations, and $4686 for treating adverse reactions. Drug costs accounted for only 55% of the total cost. Vancomycin is safe and effective, but phlebitis is underreported and significantly affects cost.