Microarray analysis of placental tissue in intrauterine growth restriction

Objective Besides foetal or maternal disorders, placental dysfunction is a major cause of intrauterine growth restriction (IUGR). Although numerous macro‐ and histopathological changes have been described, little is known about the precise aetiology and the contribution of foetal/placental genes in this disorder. Design Placental tissues of 20 IUGR and control neonates were analysed by microarray technique. Four of the regulated genes with possible relevance in the pathogenesis of IUGR and its consequences were further studied in placentas of 27 IUGR and 35 control newborns. Results Elevated gene expression of leptin, corticotrophin‐releasing hormone (CRH), and IGF‐binding protein‐1 (IGFBP‐1) in IUGR placentas could be confirmed in the larger group by real‐time PCR, whereas prolactin showed no significant difference. Accordingly, protein expression of leptin and IGFBP‐1 depicted by Western blot was elevated in IUGR, prolactin was not different. Birthweight standard deviation score (SDS) correlated negatively to leptin, IGFBP‐1, and CRH, whereas placental weight correlated only to IGFBP‐1. Leptin correlated negatively to gestational age of IUGR patients and positively to placental score, a marker of severity of impaired foeto‐placental circulation. Conclusions As confirmed in a large group of IUGR and control samples, the up‐regulated factors leptin, IGFBP‐1, and CRH may serve as candidate genes for the prediction of subsequent metabolic consequences in IUGR newborns. These three factors may not only influence growth of the foetus, but might also interact with programming of its metabolic functions, which has to be determined in an ongoing study.     

Assessing the Use of the NANDA‐International Nursing Diagnoses at the Obafemi Awolowo University Teaching Hospitals Complex,Ile Ife,Nigeria

PURPOSE. This study assessed the use of the NANDA‐I nursing diagnoses in a Nigerian hospital. METHODS. A multi‐stage sampling method was used to select seven wards and 67 nursing process booklets from the Medical, Surgical, Orthopedic, and Mental Health Units of the hospital. FINDINGS. A total of 154 nursing diagnoses were made: 50.7% were made within the first 48 hours of admission, while 35.8% were made on reassessments. The most frequently used nursing diagnoses were self‐care deficit, pain, and anxiety. CONCLUSION. The NANDA‐I nursing diagnoses are in use in Nigeria, adding support to the global use of the NANDA‐I taxonomy, but findings also suggest a need for an assessment framework informed by nursing. PRACTICE IMPLICATION. Nurses in Nigeria would benefit from training programs organized by NANDA‐I and national institutions to further refine their use of the nursing process.     

Phase II clinical trial of capecitabine in the treatment of advanced, persistent or recurrent squamous cell carcinoma of the cervix with translational research: a gynecologic oncology group study

PURPOSE: To evaluate the anti-tumor activity and adverse events of capecitabine in advanced, persistent or recurrent squamous cell carcinoma of the cervix, and to explore biomarkers with the potential to predict capecitabine response and toxicity. EXPERIMENTAL DESIGN: Eligible, consenting patients were treated with a starting dose of 2500 mg/m(2)/day or 1800 mg/m(2)/day (divided into two doses given every 12 h) for 14 days of each 21-day cycle. Prior chemotherapy was allowed only in the context of radiation "sensitization". Genotyping in the 5' and 3' ends of thymidylate synthase (TS) was performed in DNA from pretreatment blood. Relative gene expression of TS, dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) was quantified in RNA extracted from paraffin-embedded tumor. RESULTS: All patients had prior radiotherapy and 22 received a radiation sensitizer. A partial response was observed in 4 of 26 (15%) evaluable patients. An additional 35% of patients achieved stable disease while 42% experienced increasing disease. The most common serious non-hematological toxicities were gastrointestinal and dermatologic. Exploratory analyses suggested that: a germline polymorphism in the 3' or the 5' end of TS was not associated with TS gene expression, relative tumor expression of TS, DPD and TP were not correlated, and relative tumor expression of TP may predict severe anemia. CONCLUSIONS: Based on the modest response rate, this trial was closed without a second stage of accrual; single agent capecitabine was not selected for further study in advanced persistent or recurrent squamous cell carcinoma of the cervix previously treated with radiation or chemoradiation.     

Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo

BACKGROUND: Interleukin 18 (IL-18) is a cytokine with pleiotropic activity that augments T helper 1 responses and cytotoxic activity of natural killer cells. METHODS: To assess the function of IL-18 in vivo, we generated IL-18 transgenic (IL-18 Tg) mice under the control of a CD2 promoter/enhancer construct. RESULTS: Macroscopically, IL-18 Tg mice showed reduced relative liver weight compared with wild-type littermates. TUNEL assays demonstrated increased hepatocyte apoptosis, and primary hepatocytes isolated from IL-18 Tg mice exhibited an increased spontaneous apoptosis rate. Furthermore, cross linking of Fas increased significantly the apoptosis rate in hepatocytes isolated from wild- type mice but to a much lesser extent in IL-18 Tg mice, suggesting spontaneous activation of the Fas pathway in the latter mice. In fact, in vivo blockade of Fas signal transduction by an adenovirus overexpressing the dominant negative form of the Fas associated death domain rescued hepatocytes from undergoing apoptosis. Finally, adoptive transfer of CD4(+) T cells from IL-18 Tg mice but not from wild-type littermates in SCID mice resulted in severe liver failure with massive periportal fibrosis due to hepatocyte apoptosis. CONCLUSION: IL-18 plays a fundamental role in regulating hepatocyte apoptosis. Furthermore, our transgenic model provides a novel tool to study the mechanisms of IL-18 dependent liver injury in vivo.     

Eosinophilic pustule smear in the diagnosis of pediatric post-transplant eosinophilic folliculitis

Hematologic-associated eosinophilic pustular folliculitis is a subtype of eosinophilic pustular folliculitis (EPF) which develops in patients with underlying hematological malignancies after treatment with chemotherapy, bone marrow transplant (BMT), or stem cell transplant (SCT). Few cases of hematological-associated EPF have been reported in pediatric patients. Skin biopsy is considered the gold standard for diagnosis. We describe a case in which Wright staining of a pustule smear for eosinophils provided data to rapidly support a clinical diagnosis of hematologic-associated EPF.     

Evaluation of the gastrointestinal anti-motility effect of Anacardium occidentale stem bark extract: A mechanistic study of antidiarrheal activity

Diarrhea is a prevalent gastrointestinal problem associated with fatal implications. It is a huge public health concern that requires better alternatives to current drugs. This study investigated the mechanisms involved in the antidiarrheal activity of Anacardium occidentale (Ao) stem bark extract, a plant commonly used in the management of diarrhea in Nigeria. Methanolic stem bark extract of the plant was partitioned into three fractions: hexane fraction, ethyl acetate fraction (AoEF) and methanol fraction. In vitro studies on the effect of these fractions on guinea pig ileum (GPI) strips, as well as the modulatory effect of AoEF on standard agonists- and antagonists-induced GPI contraction and relaxation, revealed AoEF as the most active fraction. In vivo studies to assess the effect of AoEF on the dopaminergic, muscarinic, and serotonergic pathways were carried out using gastric emptying (GE) and gastrointestinal transit (GT) as experimental end points. AoEF was subjected to GC-MS analysis, while the identified compounds were docked with the muscarinic acetylcholine receptor M3 (CHRM3) using AutodockVina. Results indicated that AoEF inhibited GE and GT via inhibition of CHRM3. In addition, GC-MS analysis revealed the presence of 24 compounds in AoEF, while docking indicated that octadecanoic acid 2-(2-hydroxylethoxy) ethyl ester exhibited the highest binding affinity to CHRM3. This study indicated that the antidiarrheal activity of Ao is through its antimotility effect via the inhibition of the muscarinic pathway. And since none of the identified compounds exhibited higher binding affinity to CHRM3 relative to loperamide, the antimotility activity of these phytoconstituents may be via synergism.