Diamine-extended glutaraldehyde- and carbodiimide crosslinks act synergistically in mitigating bioprosthetic aortic wall calcification

BACKGROUND AND AIM OF THE STUDY: The extension of glutaraldehyde (GA) crosslinks with diamine bridges was shown previously to reduce bioprosthetic heart valve calcification to a significant degree. The aim of the present study was to investigate whether the additional crosslinking of functional carboxyl groups could augment this anticalcific effect at the low glutaraldehyde concentrations typically used in commercial heart valve production. METHODS: Entire aortic roots of medium-sized pigs were fixed after 48 h of cold storage. Crosslinking of amino-functional groups was achieved either by GA fixation alone (0.2% or 0.7%) or with an interim treatment with the diamine L-lysine (25, 50 or 100 mM; 37 degrees C; 2 days). Carboxyl groups were activated with carbodiimide (N'-{3-dimethylaminopropyl}-N-ethyl carbodiimide hydrochloride (EDC), 240 mM) and crosslinked with an oligomeric diamine (polypropylene glycol-bis-aminopropyl ether (Jeffamine), 60 mM, 230D). By permutation of treatments and combinations thereof, a total of 17 groups was compared. Aortic wall discs (12 mm diameter) were implanted subcutaneously into seven-week-old Long-Evans rats for 60 days. Tissue calcification was determined by histology and atomic absorption spectrophotometry. RESULTS: There was no significant difference in tissue calcification if either GA or carbodiimide fixation was used alone. Equally, the combined crosslinking with GA and EDC/Jeffamine did not achieve a mitigation of tissue calcification below levels seen in at least one of the two treatments alone. When commercial GA fixation was mildly diamine-enhanced with L-lysine (25 mM), additional EDC/Jeffamine crosslinking of carboxyl groups resulted in a distinct additive effect in both 0.2% (-31%; p < 0.0002) and 0.7% (-36%; p = 0.0073) GA-fixed tissue. Relative to conventional GA fixation, this combination mitigated aortic wall calcification by 43% (p < 0.0001) and 34% (p = 0.0014) in 0.2% and 0.7% GA-fixed tissue, respectively. An increase in L-lysine concentration to 100 mM further reduced calcification of 0.7% GA-fixed tissue (18.5%; p = 0.016), but had no additional effect on 0.2% GA-fixed tissue (0.6%; p = 0.463). CONCLUSION: A distinct reduction in bioprosthetic aortic wall calcification can be achieved by combining diamine-extended conventional GA fixation with a diamine-extended carbodiimide based crosslinking step.     

Research in neonatology for the 21st century: executive summary of the National Institute of Child Health and Human Development-American Academy of Pediatrics workshop. Part I: academic issues

This article presents the executive summary of the presentations and discussions at the Workshop on Research in Neonatology sponsored by the National Institute of Child Health and Human Development and the American Academy of Pediatrics Section on Perinatal Pediatrics convened in January 2004. In this article, the scientific aspects are summarized, highlighting the current knowledge gaps and identifying research priorities with a focus on emerging technologies. In a separate article, issues concerning workforce needs and shortages and board-certification requirements are presented. Full-length articles on the presented topics will be published in the Journal of Perinatology.     

Comparative evaluation of safety and immunogenicity of two dosages of an oral live attenuated human rotavirus vaccine

BACKGROUND: Rotavirus is a major cause of gastroenteritis in children worldwide and is estimated to be responsible for more than 500,000 physician visits, 50,000 hospitalizations and 20 deaths in the United States each year. OBJECTIVE: To compare the safety and immunogenicity of 2 dosages of a live attenuated oral monovalent G1 human rotavirus (HRV) vaccine in healthy infants. DESIGN/METHODS: In this randomized, double blind trial conducted in the United States and Canada, 529 healthy infants 5-15 weeks of age received HRV vaccine containing either 10 or 10 focus-forming units or placebo. Two doses were administered orally at a 2-month interval concomitantly with routine childhood vaccines. Symptoms of fever, irritability/fussiness, diarrhea, vomiting, loss of appetite and cough/runny nose were solicited for 15 days postvaccination, nonserious adverse events for 43 days postvaccination and serious adverse events throughout the study. Vaccine take was defined as appearance of serum antirotavirus IgA in postimmunization sera at a titer of > or =20 units/mL or vaccine virus shedding in any stool sample collected between the first dose and 2 months after the second dose. RESULTS: No serious adverse events considered related to vaccine were reported. The incidence of solicited symptoms was similar among treatment groups during the 15-day postvaccination surveillance periods. No significant difference in vaccine take after 2 doses (88.0% in high dose group and 81.5% in low dose group) was seen between vaccine groups (P = 0.153). CONCLUSIONS: Two doses of either dosage level of HRV vaccine administered concurrently with routine childhood vaccines to healthy infants 5-15 weeks of age were well-tolerated and were highly immunogenic.     

Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation?

OBJECTIVE: It is stated commonly that the earlier in pregnancy bacterial vaginosis is diagnosed, the greater is the increase in risk of preterm birth compared with women without bacterial vaginosis. However, this contention is based on small numbers of women. STUDY DESIGN: In this analysis of 12,937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial, the odds ratio of preterm birth (<7 weeks of gestation) for asymptomatic bacterial vaginosis-positive versus bacterial vaginosis-negative women was evaluated among women who were screened from 8 to 22 weeks of gestation. RESULTS: The odds ratio of preterm birth among bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which bacterial vaginosis was screened. The odds ratio for preterm birth did not vary significantly by gestational age at diagnosis when bacterial vaginosis was subdivided into Gram stain score 7 to 8 or 9 to 10. CONCLUSION: Although bacterial vaginosis was associated with an increased risk of preterm birth, the gestational age at which bacterial vaginosis was screened for and diagnosed did not influence the increase.     

Research on prevention of bilirubin-induced brain injury and kernicterus: National Institute of Child Health and Human Development conference executive summary. 2003

In July 2003, the National Institute of Child Health and Human Development convened a conference, "Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: Bench-to-Bedside." This article will provide a summary of presentations and discussions from this conference. The summary will focus on the identified knowledge gaps in 5 areas related to bilirubin-induced brain injury and kernicterus: 1) neurobiology and neuroimaging; 2) epidemiology and issues of clinical management; 3) methodologies for assessing clinical jaundice and direct and noninvasive measurement of serum bilirubin and hemolysis; 4) therapies for management of neonatal hyperbilirubinemia; and 5) public health surveillance and systems-based approaches to prevention.     

Frequency of uterine contractions in asymptomatic pregnant women with or without a short cervix on transvaginal ultrasound scan

OBJECTIVE: The purpose of this study was to compare the frequency of uterine contractions in asymptomatic pregnant women with and without a short cervix (< 25 mm) on transvaginal ultrasound (TVU) and to determine the additive risk of contractions on the risk of preterm birth. STUDY DESIGN: The study involved secondary analysis of a blinded observational study of asymptomatic singleton pregnancies who were at high risk for preterm birth and who received both home uterine activity monitoring daily and transvaginal ultrasound of the cervix at 22 to 24 and 27 to 28 weeks of gestation. Thresholds for the maximum frequency of uterine contractions of 4 per hour and transvaginal ultrasound cervical length of 25 mm were used for analysis. Contraction frequency was compared in women with cervical length < 25 mm and > or =25 mm and was correlated with the risk of spontaneous preterm birth at < 35 weeks of gestation. RESULTS: Of the 303 women whose pregnancy was evaluated at 22 to 24 weeks of gestation, the 39 women (13%) with a cervical length of < 25 mm had 1.6 +/- 2.7 versus 1.2 +/- 2.0 contractions per hour in the 264 women (87%) with a cervical length of > or =25 mm (P=.37). At 27 to 28 weeks of gestation (n=295 women), contraction frequency was 3.2 +/- 3.7 versus 2.8 +/- 3.1 contractions per hour in women with a cervical length of < 25 mm (n=59 women; 20%) versus those with a cervical length of > or =25 mm (n=236 women; 80%; P=.34). Among women with a short cervix, the relative risks for spontaneous preterm birth were 2.0 (95% CI, 0.95-4.2) and 2.1 (95% CI, 1.06-4.3) for women with > or =4 contractions per hour compared with women with < 4 contractions per hour at 22 to 24 and 27 to 28 weeks of gestation, respectively. Results were confirmed by logistic regression analysis. CONCLUSION: The frequency of uterine contractions in asymptomatic women was not related significantly to cervical length of < 25 mm versus > or =25 mm. Among women with a cervical length of < 25 mm at 22 to 24 or 27 to 28 weeks of gestation, there was a trend toward a 2-fold increased risk of spontaneous preterm birth when the maximum contraction frequency was > or =4 per hour, compared to < 4 per hour.     

Preoperative staging of gastric adenocarcinoma: comparison of helical CT and endoscopic US

PURPOSE: To compare the performance of helical computed tomography (CT) and endoscopic ultrasonography (US) in the preoperative staging of gastric cancer. MATERIALS AND METHODS: Fifty-one consecutive patients with a primary malignant gastric tumor (stage T2-T4) were preoperatively evaluated with both helical CT and endoscopic US within 3 days. Each tumor was staged according to the TNM classification system with both modalities. All patients subsequently underwent surgery. Results of CT and endoscopic US were compared with histologic staging of tumor invasion depth and regional lymph node metastasis. For comparison of CT and endoscopic US data, the marginal homogeneity test was used, and a P value of less than.05 was determined to indicate statistical significance. RESULTS: In comparison with histologic results, CT achieved correct T staging in 39 patients (76%) and correct N staging in 35 patients (70%). The corresponding results for endoscopic US achieved correct T staging in 44 patients (86%) and correct N staging in 45 patients (90%). There was no significant difference between T staging (P =.55) and N staging (P >.99). Because of challenging detection of wall layers, correct T staging was difficult for CT and endoscopic US in the differentiation of T2 and T3 lesions. CONCLUSION: Compared with endoscopic US, helical CT focused on the stomach provides valuable results regarding T and N staging in patients with gastric cancer.