Glutathione levels modulate domoic acid induced apoptosis in mouse cerebellar granule cells.

Exposure of mouse cerebellar granule neurons (CGNs) to domoic acid induced cell death, either by apoptosis or by necrosis, depending on its concentration. Necrotic damage predominated in response to domoic acid above 0.1 microM. In contrast, cell injury with apoptotic features (assessed by Hoechst staining and DNA laddering assay) was evident after exposure to lower concentrations of domoic acid (< or = 0.1 microM). The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptor antagonist 2,3-dihydroxy-6-nitro-sulfamoylbenzo [f] quinoxaline, but not the N-methyl-D-aspartate receptor antagonist MK-801, prevented domoic acid-induced apoptosis. To evaluate the role of oxidative stress in domoic acid-induced apoptosis, experiments were carried out in CGNs isolated from wild-type mice (Gclm (+/+)) and mice lacking the modifier subunit of glutamate-cysteine ligase, the first and rate-limiting step of glutathione (GSH) biosynthesis (Gclm (-/-)). CGNs from Gclm (-/-) mice have very low levels of GSH and were more sensitive to domoic acid-induced apoptosis and necrosis than Gclm (+/+) CGNs. The antioxidant melatonin (200 microM) and the membrane-permeant GSH delivery agent GSH ethyl ester (2.5 mM) prevented domoic acid-induced apoptosis. Domoic acid increased formation of reactive oxygen species but did not affect intracellular GSH levels. Domoic acid also increased cytosolic and mitochondrial calcium levels, increased oxidative stress in mitochondria, and altered mitochondrial membrane potential, which ultimately caused cytochrome c release, activation of caspase-3, and degradation of poly (ADP-ribose) polymerase. These results indicate that low concentrations of domoic acid cause apoptotic neuronal cell death mediated by oxidative stress.     

A decade of inequality in maternity care: antenatal care,professional attendance at delivery,and caesarean section in Bangladesh (1991–2004)

Background  

Bangladesh is committed to the fifth Millennium Development Goal (MDG-5) target of reducing its maternal mortality ratio by three-quarters between 1990 and 2015. Since the early 1990s, Bangladesh has followed a strategy of improving access to facilities equipped and staffed to provide emergency obstetric care (EmOC).     

Rectal duplications in children: two case reports and review of the literature

Duplications of the rectum are extremely rare, with only 60 cases reported in the world literature. We report two patients with cystic duplications of the rectum who underwent surgical intervention in our institution during the past 10 years. A 5-year-old white male presented with constipation and tenesmus as well as a 4-cm cystic mass that protruded from the anus when he strained to pass stool. Rectal examination and ultrasound suggested the clinical diagnosis of rectal duplication. Transanal submucosal resection of a 3-cm cystic mass adherent to the posterior rectal wall was carried out. Histologic examination revealed a rectal duplication containing zones of ciliated respiratory epithelium. The second patient, a 6-year-old white female, presented with a history of chronic constipation. A large, cystic presacral mass was detected by rectal examination and confirmed by CT scan. Complete submucosal resection of the cystic duplication was performed through a posterior trans-sacral approach. Histology revealed a rectal duplication lined by respiratory epithelium. Although duplications are generally lined by mucosa of the adjacent bowel, heterotopic mucosa, most commonly gastric or pancreatic, may be present. Rectal duplications with ectopic gastric mucosa have been previously described, but to our knowledge the presence of respiratory epithelium in a rectal duplication has never been reported. Complete resection of these lesions results in cure.Presented at the 21st Annual Meeting Canadian Association of Paediatric Surgeons Edmonton, Alberta, Canada September 21–23, 1989 Offprint requests to: A. L. Bensousson     

Emerging developmental sequelae in the 'normal' extremely low birth weight infant.

Thirty-six extremely low birth weight (less than 1000 g birth weight) children received neurodevelopmental testing in infancy (mean age = 19.1 months), and again in early childhood (mean age = 46.5 months). Children were categorized into a high-risk group (n = 20) if bronchopulmonary dysplasia and/or Grades III or IV intracranial hemorrhage were present or a low-risk group (n = 16) if neither were present. Using standardized testing and neuromotor examination, 24 (67%) of 36 children showed normal infant development. Only 11 (31%) of 36 children (P less than .005) had normal development upon reassessment in early childhood. A decline in developmental status occurred in both groups. This indicates that for the extremely low birth weight population, normal infant development is poorly predictive of continued normal development. With or without major complications, extremely low birth weight places children at substantial risk for ongoing and emerging developmental problems with age.     

The changing role of amputation for soft tissue sarcoma of the extremity in adults.

The role of amputation in soft tissue sarcoma of the extremity has decreased at Memorial Sloan-Kettering Cancer Center during the last 20 years. In an attempt to determine the reasons for this change in therapy, an analysis of two separate databases involving 1,057 patients compiled during the periods of 1968 to 1978 and 1982 to 1990 was performed. The patients requiring amputation for soft tissue sarcoma of the extremity in the two databases (n = 233) were compared in an attempt to determine any significant differences between the two time periods. The groups were specifically compared for differences in risk factors, indications for amputations and the effect a decreasing incidence of amputation in the 1982 to 1990 group had on local recurrence and overall survival between the two groups. Despite similarity of risk factors and indications for amputation, the decreased incidence of amputation during the 1982 to 1990 period was associated with a significant decrease in local recurrence after amputation and no significant change in overall survival compared with the 1968 to 1978 group. Absence of local recurrence was associated with significant improvement in survival. Possible reasons for the shift in therapy, as well as the present and future role of amputation in soft tissue sarcoma of the extremity, are discussed.     

Political economy of tobacco control in low-income and middle-income countries: lessons from Thailand and Zimbabwe. Global Analysis Project Team

Crucial to the success of the proposed Framework Convention on Tobacco Control will be an understanding of the political and economic context for tobacco control policies, particularly in low-income and middle-income countries. Policy studies in Thailand and Zimbabwe employed the analytical perspective of political economy and a research strategy that used political mapping, a technique for characterizing and evaluating the political environment surrounding a policy issue, and stakeholder analysis, which seeks to identify key actors and to determine their capacity to shape policy outcomes. These policy studies clearly revealed how tobacco control in low-income and middle-income countries is also being shaped by developments in the global and regional political economy. Hence efforts to strengthen national control policies need to be set within the context of globalization and the international context. Besides the transnational tobacco companies, international tobacco groups and foreign governments, international agencies and nongovernmental organizations are also playing influential roles. It cannot be assumed, therefore, that the tobacco control strategies being implemented in industrialized countries will be just as effective and appropriate when implemented in developing countries. There is an urgent need to expand the number of such tobacco policy studies, particularly in low-income and middle-income countries. Comprehensive guidelines for tobacco policy analysis and research are required to support this process, as is a broader international strategy to coordinate further tobacco policy research studies at country, regional and global levels.     

Precocious cervical ripening and preterm labor

A group of 8303 women was studied to determine the timing of cervical ripening. It was confirmed that these signs of cervical change can be observed several weeks before preterm births. The precocious signs of external ripening can be recognized during a vaginal examination and may be useful in predicting preterm labor.     

International expert workshop on the analysis of the economic and public health impacts of air pollution: workshop summary

Forty-nine experts from 18 industrial and developing countries met on 6 September 2001 in Garmisch-Partenkirchen, Germany, to discuss the economic and public health impacts of air pollution, particularly with respect to assessing the public health benefits from technologies and policies that reduce greenhouse gas (GHG) emissions. Such measures would provide immediate public health benefits, such as reduced premature mortality and chronic morbidity, through improved local air quality. These mitigation strategies also allow long-term goals--for example, reducing the buildup of GHG emissions--to be achieved alongside short-term aims, such as immediate improvements in air quality, and therefore benefits to public health. The workshop aimed to foster research partnerships by improving collaboration and communication among various agencies and researchers; providing a forum for presentations by sponsoring agencies and researchers regarding research efforts and agency activities; identifying key issues, knowledge gaps, methodological shortcomings, and research needs; and recommending activities and initiatives for research, collaboration, and communication. This workshop summary briefly describes presentations made by workshop participants and the conclusions of three separate working groups: economics, benefits transfer, and policy; indoor air quality issues and susceptible populations; and development and transfer of dose-response relationships and exposure models in developing countries. Several common themes emerged from the working group sessions and subsequent discussion. Key recommendations include the need for improved communication and extended collaboration, guidance and support for researchers, advances in methods, and resource support for data collection, assessment, and research.