Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms.

Subarachnoid hemorrhage is a stroke subtype with particularly bad outcome. Recent findings suggest that constrictions of pial arterioles occurring early after hemorrhage may be responsible for cerebral ischemia and - subsequently - unfavorable outcome after subarachnoid hemorrhage. Since we recently hypothesized that the lack of nitric oxide may cause post-hemorrhagic microvasospasms, our aim was to investigate whether inhaled nitric oxide, a treatment paradigm selectively delivering nitric oxide to ischemic microvessels, is able to dilate post-hemorrhagic microvasospasms; thereby improving outcome after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to experimental SAH. Three hours after subarachnoid hemorrhage pial artery spasms were quantified by intravital microscopy, then mice received inhaled nitric oxide or vehicle. For induction of large artery spasms mice received an intracisternal injection of autologous blood. Inhaled nitric oxide significantly reduced number and severity of subarachnoid hemorrhage-induced post-hemorrhage microvasospasms while only having limited effect on large artery spasms. This resulted in less brain-edema-formation, less hippocampal neuronal loss, lack of mortality, and significantly improved neurological outcome after subarachnoid hemorrhage. This suggests that spasms of pial arterioles play a major role for the outcome after subarachnoid hemorrhage and that lack of nitric oxide is an important mechanism of post-hemorrhagic microvascular dysfunction. Reversing microvascular dysfunction by inhaled nitric oxide might be a promising treatment strategy for subarachnoid hemorrhage.

Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage.

BACKGROUND Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. METHODS More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. RESULTS Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Δ at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). CONCLUSIONS Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift.

US medical students' knowledge of obstetric fistula in developing countries

Obstetric fistula is a devastating child birth injury affecting millions of women worldwide. This paper explores the knowledge and understanding of medical students at the University of Texas Health Science Center at San Antonio regarding this global public health issue. Obstetric fistula has been eradicated in most industrialized nations, and has therefore faded from view of many modern medical organizations. The United Nations Population Fund has launched a “Campaign to End Fistula” in an attempt to bring global awareness to this preventable and treatable condition. Based on a survey administered to medical students at UTHSCSA, a baseline understanding of this disorder based on current curriculum is reviewed, with the objective of improving future physicians’ awareness of obstetric fistula. Despite a low survey response rate, there was a significant association between greater knowledge about causes, treatment, and complications of obstetric fistula and advanced years in medical school. However, the fourth year medical students averaged only a 70.5 percent of correct responses on the survey, indicating room for improvement in addressing this topic during medical school. ^

OUT-OF-HOSPITAL CHILDBEARING CENTERS IN THE UNITED STATES: A DESCRIPTIVE STUDY OF THE DEMOGRAPHIC AND MEDICAL-OBSTETRIC CHARACTERISTICS OF WOMEN BEGINNING LABOR THEREIN 1972-1979

There is currently much interest in the appropriate use of obstetrical technology, cost containment and meeting consumers' needs for safe and satisfying maternity care. At the same time, there has been an increase in professionally unattended home births. In response, a new type of service, the out-of-hospital childbearing center (CBC) has been developed which is administratively and structurally separate from the hospital. In the CBC, maternity care is provided by certified nurse-midwives to carefully screened low risk childbearing families in conjunction with physician and hospital back-up.^ It was the purpose of this study to accomplish the following objectives: (1) To describe in a historical prospective study the demographic and medical-obstetric characteristics of patients laboring in eleven selected out-of-hospital childbearing centers in the United States from May 1, 1972, to December 15, 1979. Labor is defined as the onset of regular contractions as determined by the patient. (2) To describe any differences between those patients who require transfer to a back-up hospital and those who do not. (3) To describe administrative and service characteristics of eleven selected out-of-hospital childbearing centers in the United States. (4) To compare the demographic and medical-obstetric characteristics of women laboring in eleven selected out-of-hospital childbearing centers with a national sample of women of similar obstetric risk who according to birth certificates delivered legitimate infants in a hospital setting in the United States in 1972.^ Research concerning CBCs and supportive to the development of CBCs including studies which identified factors associated with fetal and perinatal morbidity and mortality, obstetrical risk screening, and the progress of technological development in obstetrics were reviewed. Information concerning the organization and delivery of care at each selected CBC was also collected and analyzed.^ A stratified, systematic sample of 1938 low risk women who began labor in a selected CBC were included in the study. These women were not unlike those described previously in small single center studies reported in the literature. The mean age was 25 years. Sixty-three per cent were white, 34 per cent Hispanic, 88 per cent married, 45 per cent had completed at least two years of college, nearly one-third were professionals and over a third were housewives. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI ^

Misoprostol in addition to routine treatment of postpartum hemorrhage: A hospital-based randomized-controlled trial in Karachi, Pakistan

Background: Postpartum hemorrhage (PPH) remains a major killer of women worldwide. Standard uterotonic treatments used to control postpartum bleeding do not always work and are not always available. Misoprostol's potential as a treatment option for PPH is increasingly known, but its use remains ad hoc and available evidence does not support the safety or efficacy of one particular regimen. This study aimed to determine the adjunct benefit of misoprostol when combined with standard oxytocics for PPH treatment. Methods: A randomized controlled trial was conducted in four Karachi hospitals from December 2005 – April 2007 to assess the benefit of a 600 mcg dose of misoprostol given sublingually in addition to standard oxytocics for postpartum hemorrhage treatment. Consenting women had their blood loss measured after normal vaginal delivery and were enrolled in the study after losing more than 500 ml of blood. Women were randomly assigned to receive either 600 mcg sublingual misoprostol or matching placebo in addition to standard PPH treatment with injectable oxytocics. Both women and providers were blinded to the treatment assignment. Blood loss was collected until active bleeding stopped and for a minimum of one hour after PPH diagnosis. Total blood loss, hemoglobin measures, and treatment outcomes were recorded for all participants. Results: Due to a much lower rate of PPH than expected (1.2%), only sixty-one patients were diagnosed and treated for their PPH in this study, and we were therefore unable to measure statistical significance in any of the primary endpoints. The addition of 600 mcg sublingual misoprostol to standard PPH treatments does, however, suggest a trend in reduced postpartum blood loss, a smaller drop in postpartum hemoglobin, and need for fewer additional interventions. Women who bled less overall had a significantly smaller drop in hemoglobin and received fewer additional interventions. There were no hysterectomies or maternal deaths among study participants. The rate of transient shivering and fever was significantly higher among women receiving misoprostol Conclusion: A 600 mcg dose of misoprostol given sublingually shows promise as an adjunct treatment for PPH and its use should continue to be explored for its life-saving potential in the care of women experiencing PPH. Trial Registration: Clinical trials.gov, Registry No. NCT00116480

Prevention and Management of Postpartum Hemorrhage

Este video de formación clínica ofrece orientación sobre el manejo activo de la tercera etapa del parto, el tratamiento de la hemorragia posparto y la hemorragia excesiva

Emergency Obstetric Care: Strategy for Reducing Maternal Mortality in Developing Countries

Twenty-five years have passed since the global community agreed in Nairobi to address the high maternal mortality by implementing the Safe Motherhood Initiative. However, every year nearly three million women die due to pregnancy related causes. This tragedy is avoidable if women have timely access to required emergency obstetric care. Emergency obstetric care refers to life-saving services for maternal and neonatal complications provided by skilled health workers. Since the beginning of the 1980’s, several efforts have been intensified to improve maternal and child health status and reducing the high morbidity and mortality. There was built on a worldwide consensus to provide improved maternal and child health care for addressing the high morbidity and mortality. All participant countries agreed to integrate emergency obstetric care services in their national health care system. Emergency obstetric care is one of the strategies for reducing the maternal mortality as pregnancy related complications are unpredictable. However, many women in developing countries do not have access to essential health care services including emergency obstetric care. Basic emergency obstetric care by skilled birth attendants or timely referral for further comprehensive emergency obstetric care can reduce maternal deaths and disabilities significantly. This paper is based on the results published in PubMed, Medline, Lancet, WHO and Google Scholar web pages from 1990 to 2013.

Practice advisory: interim guidance for care of obstetric patients during a zika virus outbreak

Zika during pregnancy has been associated with birth defects, specifically significant microcephaly. Transmission of Zika to the fetus has been documented in all trimesters; Zika virus RNA has been detected in fetal tissue from early missed abortions, amniotic fluid, term neonates and the placenta. However, much is not yet known about Zika virus in pregnancy. Uncertainties include the incidence of Zika virus infection among pregnant women in areas of Zika virus transmission, the rate of vertical transmission and the rate with which infected fetuses manifest complications such as microcephaly or demise. The absence of this important information makes management and decision making in the setting of potential Zika virus exposure (i.e. travel to endemic areas) or maternal infection, difficult. Currently, there is no vaccine or treatment for this infection.

Detection and Differentiation of Intraretinal Hemorrhage in Spectral Domain Optical Coherence Tomography.

PURPOSE The purpose of this study was to classify and detect intraretinal hemorrhage (IRH) in spectral domain optical coherence tomography (SD-OCT). METHODS Initially the presentation of IRH in BRVO-patients in SD-OCT was described by one reader comparing color-fundus (CF) and SD-OCT using dedicated software. Based on these established characteristics, the presence and the severity of IRH in SD-OCT and CF were assessed by two other masked readers and the inter-device and the inter-observer agreement were evaluated. Further the area of IRH was compared. RESULTS About 895 single B-scans of 24 eyes were analyzed. About 61% of SD-OCT scans and 46% of the CF-images were graded for the presence of IRH (concordance: 73%, inter-device agreement: k = 0.5). However, subdivided into previously established severity levels of dense (CF: 21.3% versus SD-OCT: 34.7%, k = 0.2), flame-like (CF: 15.5% versus SD-OCT: 45.5%, k = 0.3), and dot-like (CF: 32% versus SD-OCT: 24.4%, k = 0.2) IRH, the inter-device agreement was weak. The inter-observer agreement was strong with k = 0.9 for SD-OCT and k = 0.8 for CF. The mean area of IRH detected on SD-OCT was significantly greater than on CF (SD-OCT: 11.5 ± 4.3 mm(2) versus CF: 8.1 ± 5.5 mm(2), p = 0.008). CONCLUSIONS IRH seems to be detectable on SD-OCT; however, the previously established severity grading agreed weakly with that assessed by CF.

Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice

Deficiency of blood coagulation factor V or tissue factor causes the death of mouse embryos by 10.5 days of gestation, suggesting that part of the blood coagulation system is necessary for development. This function is proposed to require either generation of the serine protease thrombin and cell signaling through protease-activated receptors or an activity of tissue factor that is distinct from blood clotting. We find that murine deficiency of prothrombin clotting factor 2 (Cf2) was associated with the death of approximately 50% of Cf2−/− embryos by embryonic day 10.5 (E10.5), and surviving embryos had characteristic defects in yolk sac vasculature. Most of the remaining Cf2−/− embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare Cf2−/− neonates died of hemorrhage on the first postnatal day. These studies suggest that a part of the blood coagulation system is adapted to perform a developmental function. Other mouse models show that the absence of platelets or of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in development may be independent of its effects on blood coagulation and instead may involve signal transduction on cells other than platelets.

Maternal death and obstetric care audits in Nigeria : a systematic review of barriers and enabling factors in the provision of emergency care

Acknowledgements We would like to thank Yutaka Osakabe for co-ordinating the retrieval of full text articles. The John D. and Catherine T. MacArthur Foundation supported this study, grant number 12-100074-000-INP

Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189

The vascular endothelial growth factor (VEGF) has been shown to be a significant mediator of angiogenesis during a variety of normal and pathological processes, including tumor development. Human U87MG glioblastoma cells express the three VEGF isoforms: VEGF121, VEGF165, and VEGF189. Here, we have investigated whether these three isoforms have distinct roles in glioblastoma angiogenesis. Clones that overexpressed each isoform were derived and inoculated into mouse brains. Mice that received VEGF121- and VEGF165-overexpressing cells developed intracerebral hemorrhages after 60–90 hr. In contrast, mice implanted with VEGF189-overexpressing cells had only slightly larger tumors than those caused by parental cells and little evidence of hemorrhage at these early times after implantation, whereas, after longer periods of growth, enhanced angiogenicity and tumorigenicity were apparent. There was rapid blood vessel growth and breakdown around the tumors caused by cells overexpressing VEGF121 and VEGF165, whereas there was similar vascularization but no eruption in the vicinity of those tumors caused by cells overexpressing VEGF189, and none on the border of the tumors caused by the parental cells. Thus, by introducing VEGF-overexpressing glioblastoma cells into the brain, we have established a reproducible and predictable in vivo model of tumor-associated intracerebral hemorrhage caused by the enhanced expression of single molecular species. Such a model should be useful for uncovering the role of VEGF isoforms in the mechanisms of angiogenesis and for investigating intracerebral hemorrhage due to ischemic stroke or congenital malformations.

Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units

Objective To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews.