Is Coincidental Rhinosinusitis a Predisposing Factor for Postoperative Central Nervous System Infection After Endoscopic Endonasal Transsphenoidal Surgery?

BACKGROUND: To investigate the effect of rhinosinusitis in patients who undergo surgery via the endoscopic endonasal transsphenoidal approach (EETSA). METHODS: The authors retrospectively reviewed the medical records of patients who underwent surgery via the EETSA between February 2009 and November 2016. In total, 505 patients were included in the study. Preoperative paranasal sinus computed tomography, sellar magnetic resonance imaging, and nasal endoscopy were performed for all the patients. RESULTS: Fifteen patients without sphenoid sinusitis underwent surgery with the concomitant transsphenoidal approach and functional endoscopic sinus surgery, and showed no central nervous system (CNS) complication. During surgery via the EETSA, the presence of rhinosinusitis did not significantly affect the incidence of postoperative CNS infection (P = 0.051), except for sphenoid sinusitis (P = 0.003). Conversely, the incidence of postoperative CNS infection was not related significantly to the Lund-Mackay score or tumor size. The risk of CNS infection was 12.151-fold higher in patients with sphenoid sinusitis (95% confidence interval, 3.153-46.827; P ≤ 0.001). CONCLUSION: Surgery via the EETSA and functional endoscopic sinus surgery can be safely performed together in most patients with rhinosinusitis. However, sphenoid sinus infection appears to be a predisposing factor for postoperative CNS infection. Therefore, a separate surgical procedure for sphenoid lesions should be considered in these patients before the use of the EETSA.

Fetal heart rate regresses toward the mean in the third trimester.

The purpose of this study was to investigate the feasibility of different fetal heart rate (FHR) ranges in the nonstress test (NST) and to better understand the meaning of mild bradycardia and/or tachycardia without non-reassuring patterns. We employed the heredity to show that mild bradycardia (100-119 beats per minute, bpm) and mild tachycardia (161-180 bpm) regressed to the normal FHR range (120-160 bpm). We used linear regression to analyze FHR data from FHR tracings recorded 10 min before (NST, as the predictor) and 10 min after vibroacoustic stimulation testing (as the dependent variable). Acceleration for 15 bpm-15 seconds (Acc1515) and deceleration for 15 bpm-15 seconds (Dec1515) in the NST were also analyzed for each group. The slope of the best-fit line was the largest in the mild bradycardia group and the smallest in the normal range group. Dec1515 was most prominent in mild tachycardia and both the mild bradycardia and tachycardia groups regressed towards the mean FHR range. Therefore, we propose that both mild bradycardia and tachycardia of FHR in non-acute situations (range between 100 and 180 bpm) are not regarded a pathologic signal for clinical use.

Fetal heart rate parameters and perinatal outcomes in fetuses with nuchal cords.

AIM: The purpose of the present study was to compare and analyze differences in antepartal fetal heart rate (FHR) parameters during pregnancy and pregnancy outcomes in normal fetuses and fetuses with nuchal cord (NC). MATERIAL AND METHODS: We surveyed all non-stress test (NST) data acquired using a computerized FHR analysis system at Hanyang University Hospital between 2005 and 2008, and selected 150 cases that had NC. NSTs were performed between 37 and 42 weeks of gestation. Subjects were divided into three groups by the number of NCs: no NC and normal (n = 300), single (n = 124) and multiple NCs (n = 26). Neonatal outcomes were compared, and FHR parameters analyzed using computerized fetal monitoring system. RESULTS: FHR variability, with respect to amplitude (AMP) and mean minute range (MMR), was lower in the multiple NCs group than in the normal group (18.04 ± 0.38 vs 14.54 ± 1.10 bpm, P = 0.0207; 55.69 ± 1.22 vs 44.35 ± 3.41 ms, P = 0.0145, respectively). There were no other statistically significant differences of FHR parameters between the three groups. Baby weight was significantly lower in the multiple NCs group than in the normal group (3317 ± 24 vs 3054 ± 55; P = 0.0008), and there were no other significant differences between the groups. CONCLUSION: Computerized analysis of FHR would be helpful to assess fetal status, especially in cases of multiple NCs. Multiple NCs may be a subliminal risk factor for the babies even though they present no complications at delivery.

Estimates of induced abortion in South Korea: health facilities survey.

AIM: The aim of this study was to estimate the national rates of induced abortion in South Korea, where no quantitative national studies of abortion exist because the procedure is illegal. MATERIALS AND METHODS: A survey of 25 hospitals and 176 private clinics that provide induced abortions was conducted in 2005. The data were analyzed to estimate the nationwide rate of induced abortion. Indirect estimation methodology was used to calculate the number of annual induced abortions. RESULTS: In 2005, an estimated 342 433 induced abortions were performed in South Korea at a rate of 29.8 per 1000 women aged 15-44years. We observed that the abortion rate was higher in single women (31.6 per 1000 women) than in married women (28.6 per 1000 women). CONCLUSIONS: A significant number of induced abortions occur in both cohorts of married and unmarried women. To prevent serious physical harm to patients, the government should reconsider the practicality of the current statutes that prohibit women from seeking abortions from a qualified provider.

Fetal heart rate parameters of anencephalic fetuses according to gestational age.

OBJECTIVE: To evaluate various fetal heart rate (FHR) parameters of anencephalic fetuses and to assess the effect of the fetal nervous system on FHR according to gestational age. STUDY DESIGN: The antepartum nonstress test was performed in 25 anencephalic fetuses. Each FHR parameter was analyzed using a computerized FHR analysis system for various gestational groups, and the results were compared with results from a normal control group (N = 25). RESULTS: The mean baseline FHR of anencephalic fetuses decreased with increasing gestational age, as in normal fetuses. FHR variability increased with increasing gestational age, as in normal fetuses. CONCLUSION: In anencephalic fetuses, baseline FHR and FHR variability changed significantly with gestational age. These results suggest that the autonomic nervous system is more likely to be preserved than the central nervous system in anencephalic fetuses in spite of malformed or insufficient central nervous system.

Translocation of a cerclage band into the endocervical canal after preconception transabdominal cervico-isthmic cerclage.

A 34-year-old woman, who had a history of five spontaneous losses and failures of two McDonald purse-string cerclages, underwent a transabdominal cervico-isthmic cerclage (TCC). She became pregnant 17 months after TCC. At 35 weeks of gestation, she was admitted to our hospital due to preterm labor and delivered a healthy female baby (2270 g) by cesarean section. After delivery of the newborn infant, we found a migration of about one third of the cerclage band into the endocervical canal. Two years later, she had one further pregnancy, reached 33 weeks of gestation, and delivered a 1450 g male baby by cesarean section due to a preterm labor without any signs of infection. Although it could have been a case of pure coincidence, we take a chance to speculate that the migration of the cerclage band into the endocervical canal might have been the reason for the preterm labor, and it must have been removed at her first cesarean section and replaced by a new cerclage band for her next pregnancy.

Difference of fetal heart rate accelerations based on 10 and 15 beats per minute.

AIM: To evaluate the correlation of 10 b.p.m.-10 s and 15 b.p.m.-15 s fetal heart rate (FHR) accelerations in gestations before or after 32 weeks using computerized analysis. METHODS: A combination of amplitude and duration of FHR accelerations, 10 b.p.m.-10 s (Acc10-10) and 15 b.p.m.-15 s (Acc15-15), was analyzed according to gestational weeks between January 1999 and December 2005 in 2358 normal pregnant women who received a non-stress test at 30-42 gestational weeks. A linear regression model between Acc10-10 and Acc15-15 was estimated, and the duration difference between 10 b.p.m. and 15 b.p.m. was converted into seconds. RESULTS: Before 32 weeks of gestation, the mean number of FHR accelerations based on 15 b.p.m. was below 2.00 (mean + or - standard error, 1.58 + or - 0.19). The correlation between Acc10-10 and Acc15-15 was Acc15-15 + 2.8 = Acc10-10 (r(2) = 0.94, P = 0.0013). The mean duration difference between 10 b.p.m. and 15 b.p.m. was 36.8 s (range, 4-227 s). CONCLUSIONS: Our study verified the difference of Acc10-10 and Acc15-15 using computerized analysis as the base of visual interpretation of the definition of FHR acceleration. Acc15-15 did not occur often enough to be relevant to the definition of FHR acceleration before 32 weeks' gestation. The difference between the mean number of FHR accelerations based on 10 b.p.m. and 15 b.p.m. within a 20-min window was 2.8.

Conventional linear criteria with sample entropy in the interpretation of reactive antepartum fetal heart rate tracings.

OBJECTIVE: To compare the test duration times and rate of nonreactive results between the conventional linear reactive criteria (CLRC) and the modified nonlinear reactive criteria (MNRC) in electronic fetal heart rate (FHR) monitoring. The MNRC are the CLRC with the addition of approximate entropy or sample entropy. METHODS: One thousand women with singleton pregnancies between 30 and 37 weeks' gestation were selected. They visited Hanyang University Hospital for non-stress tests (NSTs). In these patients, FHR tracings were recorded for 50 min including the first and second 20 min of NST and 10 min of vibroacoustic stimulation test. All patients had a reactive NST with CLRC in these antepartum FHR tests. The rate of nonreactive tests and test duration times of these linear and nonlinear criteria were calculated and compared. RESULTS: The rate of nonreactive tests within a 20- and 40-min period with the MNRC (6.8 and 1.2%) was significantly lower than with the CLRC (35.2 and 10.5%, respectively; p < 0.001). To meet the reactive criteria, the mean durations of the MNRC and the CLRC were 11.47 (95% CI, 11.11-11.84) and 18.45 (95% CI, 17.79-19.12) min, respectively (p < 0.001). The MNRC led to a significant reduction in testing time of 37.8% compared to the CLRC. The rate of reactive tests using only sample entropy (0.20), calculated over 5-min segments of FHR tracings, was 88.3% (95% CI, 88.0-88.7). It was close to the results using the MNRC (93.2%) in the 20-min time window. CONCLUSION: The use of the MNRC significantly reduced the test duration times and decreased the rate of nonreactive tests when compared to the CLRC. It may be useful in providing more rapid and accurate assessment of the fetus in electronic FHR monitoring.

Utility of Human Papillomavirus Testing for Cervical Cancer Screening in Korea.

(1) Background: Cervical cancer is one of the most common cancers in Korean women. This study was performed to discover the utility of HPV (Human Papillomavirus) testing in screening of cervical lesions and to provide the prevalence of HPV and the genotype distribution in a single center of Korea. (2) Methods: A total of 15,141 women who underwent both HPV testing and cervical cytology were enrolled in this retrospective medical record review study. (3) Results: HPV testing showed higher sensitivity than cytology for the detection of histological high-grade squamous lesions. Furthermore, the sensitivity and specificity of HPV testing varied depending on the method used. The BD Onclarity™ HPV assay had higher sensitivity (90%) than the MyHPV CHIP™ kit (all types of HPV: 82%; high-risk HPV: 76%) for high-grade squamous lesions. A combination of MyHPV CHIP™ and cytology detected 90.9% (30/33) of histological high-grade squamous lesions. A combination of BD Onclarity™ HPV assay and cytology detected 96.55% (84/87) of histological high-grade squamous lesions. In addition, HPV prevalence and genotype distribution were different depending on the HPV testing method used. (4) Conclusion: HPV testing showed higher sensitivity than cytology, but the sensitivity and specificity of HPV testing had variation depending on the method used.

Differential expression of HSP90 isoforms and their correlations with clinicopathologic factors in patients with colorectal cancer.

Heat shock protein 90 (HSP90), a molecular chaperone, plays critical roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has four human isoforms; HSP90α, HSP90ß, glucose related protein 94 (GRP94), and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We evaluated the differential expression of these HSP90 isoforms in colorectal cancer (CRC) and correlated their expression levels with clinicopathological factors and patient survival rates. We performed immunohistochemical staining for HSP90α, HSP90ß, GRP94, and TRAP1 in 129 CRC tumor samples and found that HSP90α expression was significantly associated with advanced pT stage (P = 0.011) and shorter recurrence-free survival (RFS) (P = 0.010), whereas GRP94 expression was correlated with low grade (P = 0.029) and better RFS (P < 0.001). HSP90ß and TRAP1 had no prognostic impact, although HSP90ß expression was positively correlated with tumor size (P = 0.008). Based on our results, HSP90α and GRP94 are potential prognostic biomarkers of CRC. In addition, the differences in expression and functional activities among four HSP90 isoforms imply that isoform selectivity should be seriously considered when HSP90 inhibitors are studied or adopted for the treatment of CRC.

Clinical Application of 3-Dimensional Printing Technology for Patients With Nasal Septal Deformities: A Multicenter Study.

Importance: Studies have shown the controllability and porosity of polycaprolactone as well as the use of 3-dimensional (3-D) printing for nasal reconstruction in animal models. The utility of polycaprolactone with 3-D technology in nasal cartilaginous framework reconstruction in humans remains unknown. Objective: To investigate the safety and efficacy of 3-D printed, bioresorbable polycaprolactone nasal implants. Design, Setting, and Participants: This multicenter clinical trial comprised 20 patients with caudal septal deviations who underwent septoplasty, which used a 3-D printed polycaprolactone mesh, at 2 centers in South Korea. Patients were included if they were aged 18 to 74 years and had nasal septal deviations, Nasal Obstruction Symptom Evaluation scores greater than 20, and persistent nasal obstructions. Twenty-two patients met the inclusion criteria, but 2 patients were excluded before the operation. The study was conducted from July 1, 2016, to June 30, 2017. Main Outcomes and Measures: The change in total Nasal Obstruction Symptom Evaluation score between the preoperative examination and the week 12 postoperative examination was the primary outcome. Changes in bilateral nasal cavity minimum cross-sectional area and volume on acoustic rhinometry at weeks 4 and 12 after the operation as well as changes in the nasal cavity cross-sectional area at the osteomeatal unit and nasal septum angle in the paranasal sinus on computed tomography after week 12 were among the secondary outcomes. Results: Of the 20 patients included in the study, 4 (20%) were female, 16 (80%) were male, with a mean (SD) age of 34.95 (11.96) years. The preoperative and week 12 postoperative results revealed significant changes in the minimal cross-sectional areas on acoustic rhinometry (0.41 [SD, 0.39] vs -0.11 [SD, 0.18]; difference, 0.42; 95% CI, 0.23-0.61), nasal septum angles on computed tomography (11.22 [SD, 6.57] vs 2.89 [SD, 3.12]; difference, 8.33; 95% CI, 5.08-11.58), and Nasal Obstruction Symptom Evaluation scores (73.50 [SD, 19.88] vs 3.75 [SD, 6.26]; difference, 69.75; 95% CI, 59.22-80.28). The surgeons' convenience level with the procedure was favorable (visual analog scale score [SD], 90.90 [9.45]), and so were the patients' symptom improvements and satisfaction after 12 weeks (visual analog scale score [SD], 88.30 [9.87]). Conclusions and Relevance: The 3-D printed, homogeneous, composite, microporous polycaprolactone nasal implant demonstrated proper mechanical support and thinness with excellent biocompatibility and surgical manipulability. Polycaprolactone may be a clinically biocompatible material for use in various craniofacial reconstructions in the future.

Expression of miR-200c and its clinicopathological significance in patients with colorectal cancer.

MicroRNA-200c (miR-200c) is known to play a pivotal role in the regulation of epithelial-to-mesenchymal and mesenchymal-to-epithelial transition processes. However, the biological function of miR-200c in human carcinogenesis remains controversial. We examined the association of miR-200c expression with various clinicopathological factors, including KRAS mutation status and survival, in patients with colorectal cancer (CRC). The expression level of miR-200c was evaluated in 109 paired CRC and normal tissue samples using quantitative reverse transcription polymerase chain reaction. The KRAS mutation status of the CRC samples was determined using the PNAClamp™ KRAS Mutation Detection kit. Compared with the normal tissue group, miR-200c expression was significantly upregulated in the CRCs (P < .001). The expression of miR-200c was increased in CRCs with higher grade (P = .009), advanced stage (P = .042), and lymphovascular invasion (P = .003). Thirty-one CRCs (28.4%) had KRAS mutations in codon 12 or 13. CRCs with KRAS mutations had significantly higher miR-200c expression than CRCs with wild-type KRAS (P = .003). In survival analysis, high miR-200c expression was correlated with worse overall survival (P = .017) and recurrence-free survival (P = .048). Our results indicate that miR-200c is involved in tumor progression and aggressiveness in CRCs, and this oncogenic role of miR-200c may be triggered by activation of the KRAS signaling pathway.

Prognostic significance of phosphoinositide 3-kinase p110α and p110ß isoforms in non-small cell lung cancer.

The proteins p110α and p110ß are isoforms of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). Class I PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration, and their aberrant activation contributes to the oncogenesis of various human cancers. In this study, we assessed expression of p110α and p110ß in non-small cell lung cancer (NSCLC) and their association with clinicopathological factors and patient survival. Seventy-six NSCLC cases were analyzed by immunohistochemical staining for p110α and p110ß. Of the 76 tumors, 18 (23.7%) and 43 (56.6%) were classified in the high p110α and p110ß expression groups, respectively. Expression of p110α was higher in smokers compared with non-smokers (P = 0.042). No other clinicopathological factors showed significant association with p110α or p110ß expression. In univariate and multivariate survival analyses, high p110ß expression was associated with worse overall survival (OS) in stage I NSCLCs (P < 0.001), whereas the high p110α expression group had shorter OS in stage II to IV NSCLCs (P = 0.005). Our results suggest that p110α and p110ß play different roles depending on tumor stage, and that both p110α and p110ß have potential as independent prognostic biomarkers of NSCLC.

Generation of FISH probes using laser microbeam microdissection and application to clinical molecular cytogenetics.

Chromosome microdissection and the reverse FISH technique is one of the most useful methods for the identification of structurally abnormal chromosomes. In particular, the laser microbeam microdissection (LMM) method allows rapid isolation of a target chromosome or a specific region of chromosomes without damage of genetic materials and contamination. Isolated chromosomes were directly amplified by the degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR), and then the FISH probes labeled with spectrum green- or spectrum red-dUTP were generated by nick-translation. Whole chromosome painting (WCP) probes were successfully generated from only 5 copies of the chromosome. With this method, we produced 24 WCP probes for each human chromosome. We also tried to characterize a marker chromosome, which seemed to be originated from chromosome 11 on conventional banding technique. The marker chromosomes were isolated by the LMM method and analyzed by reverse FISH. We elucidated that the marker chromosome was originated from the short arm of chromosome 5 (5p11-->pter). A fully automated and computer-controlled LMM method is a very simple laboratory procedure, and enables rapid and precise characterization of various chromosome abnormalities.

Overexpression of phosphorylated 4E-binding protein 1 and its clinicopathological significances in gastric cancer.

Multiple intracellular transforming signals regulate eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1). The signals result in hierarchical phosphorylation of 4E-BP1, resulting in release of eIF4E, relieving translational repression and enhancing oncogenic protein synthesis. This study assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in gastric cancer and its correlation with clinicopathological parameters and patient survival. Tissue microarray blocks were generated from 179 gastric carcinomas and immunohistochemically stained for p-4E-BP1. The expression of p-4E-BP1 was higher in tumors that were intestinal-type (P=0.028); had a diameter smaller than 5cm (P=0.001); were lower pathological T stage (P<0.001), N stage (P=0.004), or TNM stage (P<0.001); did not have distant metastasis (P=0.027). High p-4E-BP1 expression significantly correlated with prolonged overall survival (P=0.046) and disease-free survival (P=0.035), but was not an independent prognostic factor in multivariate analysis. Our results indicate that p-4E-BP1 is more highly expressed in early gastric cancers than in advanced ones, and has limited potential as an independent prognostic biomarker in patients with gastric cancer. Larger well-controlled studies with molecular validation are warranted to elucidate more exact prognostic significance and working mechanism of p-4E-BP1 in gastric cancer.

Phosphorylated 4E-binding protein 1 expression is associated with poor prognosis in small-cell lung cancer.

Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) results in release of eIF4E, which sequentially relieves translational repression and enhances oncogenic protein synthesis. We assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in small-cell lung cancer (SCLC) and its correlation with clinicopathological factors and patient survival. This study included 117 SCLCs, which comprised 108 primary and 9 metastatic tumor tissues. We performed immunohistochemical staining for p-4E-BP1 in 117 tumors and found that 77 (66 %) were positive for p-4E-BP1 with cytoplasmic and/or nuclear immunostaining. The positive rate of p-4E-BP1 staining was significantly higher in never smokers (p = 0.034) and metastatic tumor tissues (p = 0.027). Patients with p-4E-BP1-positive SCLC tended to have poor performance status, although the difference was not statistically significant (p = 0.087). High p-4E-BP1 expression was significantly correlated with worse overall survival (OS) in all cohorts (p = 0.016). After stratification by clinical stage, p-4E-BP1 expression showed a stronger relationship with OS in patients with limited disease (p = 0.008). In addition, when stratified by treatment status, p-4E-BP1 expression was still significantly associated with worse OS in a subgroup of patients who completed treatment (p = 0.021). Our results indicate that p-4E-BP1 expression could represent oncogenic potential and contribute to the progression and aggressiveness of SCLC, suggesting it could be a candidate prognostic biomarker of SCLC, especially in limited disease.

Differential expression of heat shock protein 90 isoforms in small cell lung cancer.

Heat shock protein 90 (HSP90), a molecular chaperone, plays important roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has 4 different types of human isoforms; HSP90α, HSP90ß, glucose related protein 94 (GRP94) and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We assessed the differential expression of these HSP90 isoforms in small-cell lung cancer (SCLC) and the correlation of their expression levels with clinicopathological factors and patient survival rates. This study included 117 SCLCs, comprised of 108 primary and 9 metastatic tumor tissues. We performed immunohistochemical staining for HSP90α, HSP90ß, GRP94 and TRAP1 in 117 tumors and found that HSP90α and HSP90ß were positive in 11 (9%) and 61 tumors (52%), respectively, most of which showed weak expression, whereas GRP94 and TRAP1 were positive in 115 (98%) and 117 tumors (100%), respectively, the majority of which showed moderate or strong expression. None of the HSP90 isoforms showed significant associations with clinicopathological factors or survival status in patients with SCLC. Our results indicate that GRP94 and TRAP1 might contribute more to the carcinogenesis or biology of SCLC than HSP90α and HSP90ß, and that isoform selectivity should be considered when HSP90 inhibitors are studied or utilized for the treatment of SCLC.

The characteristics of integrins expression in decidualized human endometrial stromal cell induced by 8-Br-cAMP in in vitro.

Integrins are heterodimeric glycoproteins that have been found to undergo dynamic temporal and spatial changes in the endometrium during the menstrual cycle and in early pregnancy. Specificity of integrins is known to be different in human endometrial stromal cells and decidual cells. These shifts of integrins suggested to play an important role in embryo implantation and can be modulated by progesterone, cAMP derivatives, and cytokines. The mechanisms of decidualization and its precise physiological role are still not clearly understood and in vitro systems could provide an alternative that overcomes limitations of studying such complex biological phenomena in vivo at the time of implantation. This study was undertaken to establish an in vitro model system for human decidualization using 8-bromo-cAMP and to investigate the characteristics of stromal integrin expression in vitro by 8-Br-cAMP. Endometrial stromal cells were isolated and cultured, and then were induced to decidualize by 0.5 mM 8-Br-cAMP for 15 days. Immunofluorescence staining and flow cytometric analyses of the integrin subunits (alpha1, alpha4, alpha5, alpha6, beta1 and alphavbeta3) were performed at day 9. In the presence of 8-Br-cAMP, the staining intensity of alphavbeta3 was significantly higher than control and measurements for alpha1, alpha4, alpha5, alpha6, and beta1 were similar. Immunofluorescent localization of the integrins reflected the differences obtained from the flow cytometric analyses described above. In summary, the expression of alphavbeta3 integrin increased in stromal cells in vitro decidualized by 8-Br-cAMP and this up-regulation of alphavbeta3 integrin expression during decidualization might influence on human implantation.

Autonomous control of terminal erythropoiesis via physical interactions among erythroid cells.

In vitro erythropoiesis has been studied extensively for its application in the manufacture of transfusable erythrocytes. Unfortunately, culture conditions have not been as effective as in vivo growth conditions, where bone marrow macrophages are known to be a key regulator of erythropoiesis. This study focused on the fact that some erythroblasts are detached from macrophages and only contact other erythroblasts. We hypothesized that additional factors regulate erythroblasts, likely through either physical contact or secreted factors. To further elucidate these critical factors, human erythroblasts derived from cord blood were cultured at high density to mimic marrow conditions. This growth condition resulted in a significantly increased erythroid enucleation rate and viability. We found several novel contact-related signals in erythroblasts: intercellular adhesion molecule-4 (ICAM-4) and deleted in liver cancer-1 (DLC-1). DLC-1, a Rho-GTPase-activating protein, has not previously been reported in erythroid cells, but its interaction with ICAM-4 was demonstrated here. We further confirmed the presence of a secreted form of human ICAM-4 for the first time. When soluble ICAM-4 was added to media, cell viability and enucleation increased with decreased nuclear dysplasia, suggesting that ICAM-4 is a key factor in contact between cells. These results highlight potential new mechanisms for autonomous control of erythropoiesis. The application of these procedures to erythrocyte manufacturing could enhance in vitro erythrocyte production for clinical use.

Comparison of fetal heart rate patterns using nonlinear dynamics in breech versus cephalic presentation at term.

BACKGROUND: It has been reported that breech fetuses have inferior neurological outcomes regardless of mode of delivery, raising the possibility that in utero neurological impairment is more frequent in breech fetuses, possibly contributing to malpresentation. AIMS: To assess differences between the cardiovascular autonomic nervous systems (ANSs) of breech and cephalic fetuses using nonlinear dynamic indices of fetal heart rate (FHR) variability. STUDY DESIGN AND SUBJECTS: This study included 86 fetuses with breech presentation and 173 fetuses with cephalic presentation, with no other maternal or fetal problems. We analyzed FHR variability and spectral indices as markers of ANS behavior. We used nonlinear dynamic indices to represent the complexity of heart rate regulation, as well as correlation dimension as a chaotic index of the cardiovascular control system. RESULTS: One of FHR parameters (Mean minute range) was significantly lower in breech than cephalic fetuses (p=0.0294). However, there were no other significant differences in any linear or nonlinear indices, nor in clinical outcomes, between breech and cephalic fetuses. CONCLUSION: Our data suggest that breech fetuses have neither more active ANS nor less active complexity control systems than do cephalic fetuses. This indicates that the neurologic maturation of breech fetuses is not inferior to cephalic ones. The practical implication of these findings is that the nervous system integrity of breech fetuses may not result directly in neonatal complications.