Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.     

Mortality trends in systemic sclerosis in France and USA, 1980–1998: an age-period-cohort analysis

We compared trends of Systemic Sclerosis (SS) mortality in France and the USA over the period 1980–1998 and used an Age-Period-Cohort (APC) model to adjust on the age at death of SS patients. All deaths coded with SS as an underlying primary or secondary cause in the national French and US mortality databases from 1980 to 1998 were included in the analysis. SS age-standardized mortality rates increased from 7.2 to 10.3/million in US women (+43%), and from 3 to 3.9/million in French women (+22%). Most of the increase occurred in senior women. In contrast, SS age-standardized death rates remained stable among US men (around 3/million) and French men (around 2/million). In US women, the APC analysis shows a growing cohort effect between 1900 and 1940, tending to stabilize for following cohorts. Similar findings were obtained to a lesser extent in French women. In conclusion, SS mortality rates increased by more than 40% between 1980 and 1998 in the USA, mostly in women born between 1900 and 1940. Whether these trends reflect rising incidence of SS need to be documented. The observed dissimilarity between genders and countries underline that environmental exposure and gender-related factors likely play a major etiological role. Stabilization in the following birth cohorts suggests that the increase of mortality observed since 1980 may slow down in the near future.     

Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium

Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy for treating ischemic heart failure, but data concerning the distribution and retention of transplanted cells remain poor. We investigated the short-term myocardial retention of BMSCs when these cells are directly injected within necrotic or intact myocardium. 111Indium-oxine-labeled autologous BMSCs were injected within either 1-month-old infarction (n = 6) or normal myocardium (n = 6) from rats. Serial in vivo pinhole scintigraphy was scheduled during 1 week in order to track the implanted cells. The myocardial retention of BMSCs was definitely higher in myocardial infarction than in normal myocardial area (estimated percent retention at 2 h: 63 +/- 3% vs. 25 +/- 4%, p < 0.001) and the estimated cardiac retention values were unchanged in both groups along the 7 days of follow-up. On heart sections at day 7, labeled BMSCs were still around the injection site and appeared confined to the scarred tissue corresponding either to the infarct area or to the myocardium damaged by needle insertion. BMSCs have a higher retention when they are injected in necrotic than in normal myocardial areas and these cells appear to stay around the injection site for at least a 7-day period.     

Low molecular weight fucan prevents transplant coronaropathy in rat cardiac allograft model

INTRODUCTION: Transplant arteriosclerosis is the main cause of long-term failure after cardiac transplantation. Vascular rejection is thought to be due to intimal proliferation occurring in response to arterial wall immune-mediated injury. A low molecular weight fucan (LMWF) compound, a sulfated polysaccharide, has been demonstrated to increase plasma levels of stromal cell-derived factor 1 (SDF-1) and consequently to mobilize bone marrow-derived vascular progenitor cells (BMVPC). The aim of this study was to evaluate the capacity of LMWF to prevent coronary intimal proliferation in a rat cardiac allograft model. METHODS: Heterotopic abdominal cardiac graftings were performed in Brown Norway (BN) and Lewis (LEW) rats. Animals were divided into 4 groups of 10 rats. Two groups were treated intramuscularly with LMWF (5 mg/kg/day) (one BN to BN isograft group, and one BN to LEW allograft group); and two control groups were LMWF-untreated (one BN to BN isograft group and one BN to LEW allograft group). All animals were treated by cyclosporin (15 mg/kg/day) sub-cutaneously and sacrificed at day 30. The cardiac grafts were assessed by morphometry of structural parameters and by histological and immunohistochemical analyses. RESULTS: All cardiac isografts were devoid of any coronary and parenchymal lesions. In contrast, the majority of untreated allografts developed coronary intimal proliferation in close association with intimal and adventitial inflammatory CD68(+) cell infiltration. Further, the parenchyma exhibited large areas of actin(+) cells (myofibroblasts) of recipient origin colocalized with the CD68(+) infiltrating cells. Interestingly, all LMWF-treated allografts were well protected against coronary and parenchymal lesions and the coronary arteries exhibited an intimal monolayer of flat cells, which however were CD34 negative. CONCLUSION: treatment with LMWF appeared very effective in this rat cardiac allograft model to prevent arterial and parenchymal lesions occurring in response to alloimmune injury. However this protective effect does not appear to depend on mobilization of bone marrow-derived cells.     

Complete unilateral ureteral obstruction in the fetal lamb. Part I: long-term outcomes of renal hemodynamics and anatomy

PURPOSE: We evaluated the long-term consequences of complete fetal UUO on renal hemodynamics and anatomy. MATERIALS AND METHODS: A total of 26 fetal lambs underwent surgical UUO at 90 days of gestation and 14 twin matched animals served as controls. Synchronous bilateral ARBF was measured using mean transit time technology. Standard anatomical analysis, including evaluation of RPV, was performed in the kidneys. Measurements were done 10, 20 and 40 days following UUO in groups 1 to 3, respectively and in 1-month-old lambs in group 4. RESULTS: All obstructed kidneys underwent typical hydronephrotic transformations with a progressive decrease in parenchymal volume compared to that of contralateral and control kidneys. ARBF in obstructed kidneys was significantly decreased compared to their contralateral counterparts in all groups (p <0.01). Comparing ARBF to RPV showed that the decrease in ARBF was proportional to the loss of parenchymal volume in fetal obstructed kidneys but it remained significant in lambs (p <0.05). CONCLUSIONS: Complete UUO alters ARBF, while vascularization of the remaining renal parenchyma is maintained in fetuses. Profound impairment of the renal arterial supply observed in lambs may be due to physiological changes linked to birth.     

Complete unilateral ureteral obstruction in the fetal lamb. Part II: Long-term outcomes of renal tissue development

PURPOSE: We analyzed the dynamics of the renal tissue response to experimental fetal urinary flow impairment concerning renal morphology, extracellular matrix composition, regulators of connective tissue degradation and PAX2 protein expression. MATERIALS AND METHODS: A total of 26 fetal lambs underwent surgical unilateral ureteral obstruction at 90 days of gestation and 14 twin matched animals served as controls. Kidneys were harvested 10, 20 and 40 days after the prior procedure in groups 1 to 3, respectively and in 1-month-old lambs (group 4). Morphological analysis was done using light microscopy. Picrosirius red staining was used to evaluate the area occupied by extracellular matrix components. Collagen I, III and IV, alpha-smooth muscle actin, MMP-1, 2 and 9, TIMP-1 and 2 and PAX2 protein were assessed using immunochemistry. RESULTS: All obstructed kidneys were hydronephrotic without dysplasia. Hypoplasia resulting from a decreased NGG was observed. The inflammatory response to obstruction was poor in fetal obstructed kidneys. From 10 days after obstruction interstitial fibrosis was noted and confirmed by an increase in picrosirius red staining. In obstructed kidneys immunochemistry showed an increase in collagen deposition beginning from the papillae and extending through the whole parenchyma. Aberrant interstitial collagen IV deposition was observed. The increase in alpha-smooth muscle actin staining was mainly localized in the blastema and interstitial cells in obstructed kidneys. MMP and TIMP immunostaining was mainly present in tubules throughout the whole nephrogenic period and persisted in mature kidneys. Beginning from 20 days after obstruction a progressive increase in MMP and TIMP expression was noted. This was associated with ectopic expression in the medullary tubules. PAX2 protein was highly expressed in the nephrogenic zone, decreasing progressively to being markedly decreased in control lamb kidneys. No difference was found in PAX2 expression during the fetal period when comparing unobstructed and obstructed kidneys, it but remained strongly expressed in the dilated collecting ducts of obstructed lambs. CONCLUSIONS: Complete unilateral ureteral obstruction performed in fetal lambs at 90 days of gestation led to pure hydronephrotic transformation, hypoplasia and a marked increase in connective tissue deposition. Inflammatory infiltrates and PAX2 dysregulation were not seen as having a decisive role in these modifications.     

Improved detection of episomal Banana streak viruses by multiplex immunocapture PCR

Banana streak viruses (BSV) are currently the main viral constraint to Musa germplasm movement, genetic improvement and mass propagation. Therefore, it is necessary to develop and implement BSV detection strategies that are both reliable and sensitive, such as PCR-based techniques. Unfortunately, BSV endogenous pararetrovirus sequences (BSV EPRVs) are present in the genome of Musa balbisiana. They interfere with PCR-based detection of episomal BSV in infected banana and plantain, such as immunocapture PCR. Therefore, a multiplex, immunocapture PCR (M-IC-PCR) was developed for the detection of BSV. Musa sequence tagged microsatellite site (STMS) primers were selected and used in combination with BSV species-specific primers in order to monitor possible contamination by Musa genomic DNA, using multiplex PCR. Furthermore, immunocapture conditions were optimized in order to prevent Musa DNA from interfering with episomal BSV DNA during the PCR step. This improved detection method successfully allowed the accurate, specific and sensitive detection of episomal DNA only from distinct BSV species. Its implementation should benefit PCR-based detection of viruses for which homologous sequences are present in the genome of their hosts, including transgenic plants expressing viral sequences.     

Postmenopausal hormone therapy and cardiovascular disease: an overview of main findings

Cardiovascular disease has emerged as a leading cause of death in women. In recent years, significant attention has been paid to the potential benefits of hormone therapy on chronic diseases such as cardiovascular disease. Large prevention trials failed to confirm the cardioprotective effect of estrogen. The divergent findings from observational and randomized clinical studies are summarized and reasons for the different results are postulated. Use of estrogen alone or estrogen opposed with progestins is not indicated for the prevention of cardiovascular disease and may even increase the risk of stroke. Oral estrogen increases venous thromboembolism events. Recent data suggest that transdermal estrogens are safe with respect to venous thromboembolism. Current data have limited ability to investigate the wide variety of hormone treatments available. Clinical research should be continued to assist patients and clinicians in making treatment decisions on the basis of an individual's benefits and risks.