Advance distribution of misoprostol for the prevention of postpartum hemorrhage in South Sudan

Objective

To determine if high uterotonic coverage can be achieved in South Sudan through a facility- and community-focused postpartum hemorrhage (PPH) prevention program.

Methods

The program was implemented from October 2012 to March 2013. At health facilities, active management of the third stage of labor (AMTSL) was emphasized. During prenatal care and home visits, misoprostol was distributed to pregnant women at approximately 32 weeks of pregnancy for the prevention of PPH at home births. Data on uterotonic coverage and other program outcomes were collected through facility registers, home visits, and postpartum interviews.

Results

In total, 533 home births and 394 facility-based births were reported. Misoprostol was distributed in advance to 787 (84.9%) pregnant women, of whom 652 (82.8%) received the drug during home visits. Among the women who delivered at home, 527 (98.9%) reported taking misoprostol. A uterotonic for PPH prevention was provided at 342 (86.8%) facility-based deliveries. Total uterotonic coverage was 93.7%. No adverse events were reported.

Conclusion

It is feasible to achieve high coverage of uterotonic use in a low-resource and postconflict setting with few skilled birth attendants through a combination of advance misoprostol distribution and AMTSL at facilities. Advance distribution through home visits was key to achieving high coverage of misoprostol use.     

Induction of apoptosis in murine tumors by cyclophosphamide

Whereas there have been several recent reports of the induction of apoptosis by chemotherapy agents in cell culture systems, much less is known about the role of this mode of cell death in tumors treated in vivo. We therefore quantitated the proportion of apoptotic cells induced as a function of time and dose in two murine tumors treated with cyclophosphamide in vivo. The two tumors were a mammary adenocarcinoma, MCa-4, and an ovarian adenocarcinoma, OCa-1. The percent apoptosis was scored from stained histological sections of the tumors using a system based on the characteristic features of the apoptotic nuclei. The kinetics of apoptosis development were determined over a 5-day period following treatment of the mice with 200 mg/kg. The percent apoptosis peaked between 10–18 h in both tumors and then slowly declined to background levels by 5 days after treatment. The dose responses showed that even much lower doses, 25 mg/kg, could induce significant apoptosis and that the proportion of apoptotic cells plateaued at doses higher than 100 mg/kg. These results are compared and contrasted with our previous reports on apoptosis induction in these same tumors with ionizing radiation.The Work reported in this paper was supported by research grants CA-06294 and CA-16672 awarded by the National Cancer Institute, Department of Health and Human Services, and by the Katharine Unsworth Memorial Fund     

Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma

A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.     

Progression of corpus callosum atrophy in Alzheimer disease

BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.     

Frontal brain activity predicts individual performance in an associative memory exclusion test

Event-related brain potentials (ERPs) were recorded from 24 young adults during a recognition test including Old, New, and Recombined pairs composed of two words studied in different pairs. Recombined pairs called for a response of 'new'. Task difficulty was increased by repetition of some words during the study phase; a subject might study tower/pie, puppet/pie, drill/wreath and bee/wreath (pairs with a Common word), and at test, encounter the Common Recombined pair of puppet/wreath (in addition to Unique Recombined pairs composed of two words studied once). Individual accuracy in the Recombined conditions varied widely, but was unrelated to general memory ability as indexed by accuracy on the Old and New pairs. Posterior brain potentials showed graded amplitudes dependent on the oldness of both the individual words and their combinations (Old > Recombined > New, and Common > Unique), but were also unrelated to accuracy in the Recombined conditions. Amplitudes of ERPs recorded over prefrontal scalp accounted for a large proportion of the individual variability in differentiating studied combinations of words from recombinations of studied elements. The experimental design differentiates three possible roles of prefrontal cortex in source or associative memory tests: resolving a conflict between familiarity and a response of 'new', extended memory search, and evaluation of ambiguous memory signals.     

Hepatitis B in the family

During a 3-year period (1992–1995), 239 index cases of hepatitis B virus (HBV) infection and 459 members of their households from the Osijek-Baranja county were examined. The aim of the study was to determine the spread of HBV infection in the families with a member verified as a virus carrier, and to identify the family members with the highest risk of infection according to kinship degrees. The retrospective and prospective methods were used in the study. The probable route of infection was assessed by the use of an epidemiologic questionnaire, and the serologic status of the study subjects concerning infection with HBV was determined by enzyme immunoassays (HBsAg, anti-HBs, anti-HBe and anti-HBc). The first member of a family identified as a virus carrier was considered an index case. HBV infection was demonstrated in 334 (47.85%) out of a total of 698 subjects. Only 21 (6.28%) of the 334 subjects with verified HBV infection developed the clinical picture of acute hepatitis B. The ratio of clinically manifest vs inapparent infection was 1:16. Serologic traces of infection were detected in 95 of the 459 family members of the index cases, yielding a mean rate of the infection among the virus carrier family members of 20.70%.