Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.

Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.

Biomagnetic activity and non linear analysis in obstetrics and gynecology in a Greek population.

This article reports the application of non-linear analysis to biomagnetic signals recorded from fetal growth restriction, fetal brain activity, ovarian lesions, breast lesions, umbilical arteries, uterine myomas, and uterine arteries in a Greek population. The results were correlated with clinical findings. The biomagnetic measurements and the application of non-linear analysis are promising procedures in Obstetrics and Gynecology.

Hypertensive disorders in pregnancy: risk factors and epidemiologic analysis.

OBJECTIVE: To measure the incidence of preeclampsia-eclampsia and its perinatal mortality as they appear in the two major ethnic groups in Thrace: Christian Orthodox and Muslims. STUDY DESIGN: Incidence and perinatal mortality of preeclampsia-eclampsia were studied retrospectively on all women managed in our clinic for hypertensive disorders in pregnancy who were delivered of a stillborn or healthy neonate between 1986 and 1999. We also compared the prevalence of certain risk factors of the disease as they appear in the above-mentioned distinct ethnic groups. RESULTS: The total incidence of preeclampsia-eclampsia in Thrace was 2.3% and the total perinatal mortality 6.4%. Both variables presented higher values and severe preeclampsia-eclampsia had greater prevalence in the Muslim population. Most risk factors presented statistically significant differences between Christians and Muslims (chi2 test, p < 0.05). CONCLUSIONS: There was an ethnic variation in most epidemiologic variables of hypertensive disorders in Thrace between Christians and Muslims.

Biomagnetism in perinatal medicine. Our experience in Greece.

This is a report on our experience in the application of biomagnetism in perinatal medicine. We provide a brief description of our research work in fetal magnetoencephalography and fetal magnetocardiography in normal, preeclamptic and IUGR pregnancies, together with hemodynamics of the umbilical cord and uterine arteries, providing a new approach to biomagnetism as a non invasive imaging modality in the investigation of perinatal complications.

Magnetic field profiles in normal human breast during the menstrual cycle.

OBJECTIVE: To investigate the subtle magnetic fields produced by living normal breast tissue during the menstrual cycle. METHODS: The magnetic activity of the breast was recorded in four young women, 26-28 years old; two had regular and two irregular menstrual cycles. The recordings were accomplished with a biomagnetometer and covered two complete menstrual cycles. The results were correlated with estrogen and progesterone levels on days 7, 14 and 21 of the menstrual cycle. RESULTS: The magnetic breast recordings in the two young women with the regular cycling endometrium showed a biphasic magnetic curve, apparently corresponding to the proliferative and secretory phase of the menstrual cycle. By contrast, the two young women with irregular menstrual cycles showed a monophasic magnetic curve. CONCLUSION: It is suggested that a biphasic, but not a monophasic, pattern of magnetic activity in the breast is indicative of an ovulatory endometrial cycle.

Biomagnetism in gynaecologic oncology. Our experience in Greece.

Our experience in the application of biomagnetism in gynaecologic oncology is presented. We provide a brief description of our research work in the investigation of biomagnetic activity in benign and malignant ovarian and breast diseases, and an evaluation of uterine myomas, providing a new approach of biomagnetism as a non invasive imaging modality for assessing gynaecologic tumours.

Magnetoencephalography and magnetocardiography in neonates. Our experience in Greece.

This study reports our experience in the application of magnetoencephalography (MEG) and magnetocardiography (MCG) in neonates. Results gained from our studies, lead us to believe that MEG and MCG could provide clinical practice with non-invasive, rapid and easy to perform methods, which could be adjuncts to conventional methods for the evaluation of neonatal brain and heart function.

Epidemiology of congenital anomalies in different ethnicities.

PURPOSE OF INVESTIGATION: To study the prevalence and the epidemiologic characteristics of major congenital anomalies (MCAs) in two different populations in Thrace-Greece. METHODS: The ethnic origin of all mothers who delivered in our department and the types of MCAs were determined. We compared the frequencies of MCAs between Christians and Muslims. The chi-square test, t-test, binary and multinomial logistic regression analysis were performed. RESULTS: The prevalence of MCAs was significantly higher in Muslims as compared to Christians (51/4,028 (12.78%) vs 49/5,994 (8.17%), p = 0.035). However, the frequencies of each type of MCA in the total number of deliveries between the two groups did not differ significantly. The central nervous system malformations were most frequently associated with perinatal mortality. CONCLUSION: This is the first study in Greece showing that there is probably a higher prevalence of MCAs in Muslims as compared to Christians, although it can not be elucidated whether this increased risk is related to specific differences between them.

Correlation between biomagnetic and Doppler findings of the uterine artery in normal and preeclamptic pregnancies.

OBJECTIVES: To elucidate the hemodynamics of the uterine artery in normal and abnormal pregnancies by use of Doppler ultrasound and SQUID biomagnetometry. METHOD: Two hundred and three women (gestational age 28-42 weeks) were included in the study. Forty-three of them had preeclampsia and/or intrauterine growth restriction and 160 were normal. Uterine artery waveform measurements were evaluated by use of pulsatility index (PI) (normal value PI<1.45). Biomagnetic signals of uterine arteries were recorded and analyzed with Fourier analysis. The biomagnetic signals were distributed according to spectral amplitudes as high (140-300 fT/ radicalHz), low (50-110 fT/ radicalHz) and borderline (111-139 fT/ radicalHz). RESULTS: There was a statistically significant difference between normal and abnormal pregnancies concerning the waveform amplitudes (p < 0.001) and the PI index (p < 0.001). Specifically, we noticed high biomagnetic amplitudes in most normal pregnancies (92.5%) and low biomagnetic amplitudes in most preeclamptic cases (90.7%). CONCLUSIONS: Our study results indicated that biomagnetic measurements of uterine artery might prove to be useful in the evaluation of the fetal well being, especially in cases of preeclampsia and intrauterine growth restriction.

Proliferative breast disease: epidemiologic aspects, and cytologic diagnosis.

PURPOSE: The aim of the present study is to describe the prevalence of proliferative breast lesions in cases of benign and malignant tumors of the breast as well as to assess the contribution of rapid intraoperative imprint cytology in the diagnosis of proliferative breast disease. METHODS: Frozen section and intraoperative imprint cytology were performed on breast tissue biopsies from 486 breast cancer patients who underwent primary surgical treatment. Imprints were stained either by the Papanicolaou (Pap) or the May Grünwald-Giemsa (MGG) or the Hematoxylin eosin (HE) technique. Cytologic diagnoses were compared to the histopathologic ones from paraffin sections. RESULTS: Sclerosing adenosis was the most common finding in benign breast biopsies while in breast cancer the prevalence of the lesion was reduced by half. On the other hand, atypical hyperplasias in malignant biopsies were almost twice as many as in benign ones. Imprint cytology presented high sensitivity and specificity (99% and 96% respectively) in distinguishing benign proliferative from malignant lesions as a whole, but regarding atypical hyperplasias the specificity was significantly reduced (76% vs 96%). CONCLUSION: Clarification of cytologic diagnostic criteria and expertise in cytologic interpretation could show off intraoperative imprint cytology as a useful and inexpensive diagnostic tool providing the surgeon with prompt and accurate information regarding the nature of breast lesions.

Chaotic analysis approach in neonatal magneto-encephalography.

The aim of this study was to investigate the presence of any non-linearity in the magneto-encephalographic recordings (MEG) in neonates born to pre-eclamptic mothers in comparison with the ones born to mothers having uncomplicated pregnancies, in order to find out differences in the mechanisms underlying their brain waves. Our study population consisted of 40 term neonates who were delivered normally, without any clinical signs of brain damage. Thirty of them had a normal pregnancy and labour with normal Apgar scores, umbilical cord pH, and birth weight, while 10 neonates had suffered a pre-eclamptic pregnancy. The above analysis of the MEG in the neonatal pre-eclamptic brain showed a lower dimension complexity as compared with the normal neonatal brain and a lower first Lyapunov exponent which means lower information processing. The non-linear analysis of the MEG activities in neonates may offer important perspectives to understand significant features of their brain function.

Laparoscopic evaluation of congenital absence of the uterus. a case report.

Anatomic gynecologic anomalies, including congenital absence of the uterus, occur with surprising frequency in referral practice of reproductive endocrinology and reproductive surgery. Female individuals with uterus agenesis have normal external genitalia and, therefore, the diagnosis is rarely made in infancy. We report a case of congenital absence of the uterus in a young woman 25 years old, presenting with primary amenorrhea. The patient had a normal karyotype and normal secondary sex characteristics. Sex hormones were within normal limits, indicating normal function of the hypothalamic-pituitary-ovarian axis. The diagnosis was set by bimanual gynecologic examination, which was followed by vaginal ultrasound examination. The patient underwent a laparoscopic investigation, which revealed the absence of the uterus and the presence of small rudimentary uterine horns, connected to normal fallopian tubes. Ovarian morphology was bilaterally normal. In conclusion we believe that every patient with genital tract abnormalities has to be dealt with individually, depending on the patient's anatomy, desires and age.

Fetal small bowel obstruction: report of two cases.

Fetal small bowel obstruction is usually diagnosed by sonography in the late second or early third trimester. We report two such cases of different etiology: a case of meconium ileus due to cystic fibrosis and a case of intestinal atresia. The only sonographic finding that allowed differentiation between them was the echogenic bowel in the case of cystic fibrosis.

Chaotic and periodic analysis of fetal magnetocardiogram recordings in growth restriction.

OBJECTIVE: We studied how chaotic and periodic heart rate dynamics differ between normal fetuses (n = 19) and intrauterine growth restricted fetuses (n = 11) at 34 to 37 weeks of gestation. We quantified the chaotic dynamics of each heart rate time series obtained by fetal magnetocardiography (FMCG) using correlation dimension. METHODS: The FMCG was recorded digitally by a single-channel biomagnetometer in an electrically shielded room of low magnetic noise. The position of the fetal heart was determined using ultrasonography. RESULTS: The correlation dimension was significantly lower in IUGR than in normal fetuses (p < 0.001, t-test). The periodic dynamics were also obtained by FMCG and measured by power spectrum. The low-frequency components and therefore the periodicity of the low-frequency range were significantly higher in IUGR than in normal fetuses (p < 0.001, t-test). CONCLUSIONS: The analysis of FMCG recordings may offer important perspectives to understand significant features of the heart function of the fetuses. This technique improves the recognition of IUGR fetuses over healthy ones and may help improve perinatal morbidity and mortality.

Removal of endometrial polyps by use of grasping forceps and curettage after diagnostic hysteroscopy.

PURPOSE OF INVESTIGATION: To determine the therapeutic efficacy of the use of gall stone forceps and curettage in endometrial polyps removal, after their detection with diagnostic hysteroscopy. METHODS: From 1997 to 2001, we conducted a prospective study in 53 patients who presented at our department for menstrual disorders, infertility problems or postmenopausal bleeding and in whom endometrial polyps were detected by hysteroscopy. All patients received general anesthesia and after hysteroscopic detection of the polyps' location, their removal was attempted by use of Desjardins gall stone forceps and curettage. Immediately after the procedure, a second hysteroscopy was performed in order to detect remnants of the polyps. RESULTS: Fifty patients presented with only one polyp, two with two polyps and one with three polyps. The mean diameter of the polyps ranged from 0.5 to 3 cm. The hysteroscopic appearance of all polyps was not suggestive of malignancy. During the second hysteroscopy we found parts or whole polyps in five and two cases, respectively, accounting for a therapeutic success of 86.8%. The hospitalization time for all patients was 24 hours and occurred no intraoperative or postoperative complications. CONCLUSION: Our method seems to be safe, with low cost and sufficient therapeutic outcome and could be used in hospitals with availability of diagnostic hysteroscopy only.

Correlation between biomagnetic and Doppler findings of umbilical artery in fetal growth restriction.

OBJECTIVE: To assess the value of biomagnetic recordings of the umbilical artery over Doppler ultrasound screening in order to predict complications of impaired uteroplacental blood flow in fetuses with intrauterine growth restriction (IUGR). METHODS: Our study population included 11 IUGR preeclamptic (34-37-weeks gestation; birth weight 1969 +/- 129 g) and 19 normal pregnancies (34-37-weeks gestation; birth weight 3195 +/- 229 g). Umbilical artery Doppler ultrasound waveform measurements were expressed in terms of pulsatility index (PI). Biomagnetic signals (waveforms) recorded from the IUGR umbilical artery were expressed in terms of magnetic power spectral amplitudes. RESULTS: In all cases, the frequency band considered was 2 to 7 Hz. The spectral amplitudes were low (mean: 117+/-24 fT/ radical Hz) in most (90.9%) IUGR pregnancies and high (mean: 224+/-37 fT/ radical Hz) in most normal pregnancies (89.5%). There was a statistically significant difference between normal and IUGR pregnancies with respect to spectral amplitudes (p < 0.0001), Doppler PI (p < 0.0005), pH (p < 0.0005) and Apgar score (p < 0.0005). Multiple linear regression analysis revealed an influence of PI, pH and Apgar scores on the biomagnetic values (ANOVA: p < 0.0005). CONCLUSION: Our data imply that biomagnetic values of the umbilical artery flow could prove to be a helpful method for the evaluation of fetal well being especially in pregnancies complicated with preeclampsia and growth restriction.

Attitudes towards contraceptive pill use in two different populations in Thrace, Greece.

OBJECTIVE: To investigate the differentiation in attitudes towards contraceptive pill use in two different populations in Thrace, Greece. A retrospective study on representatives of the two major religious subgroups in Thrace: 127 Orthodox Christians and 120 Muslims. The questionnaire was designed to investigate women's opinions concerning the possible beneficial and adverse effects of the contraceptive pill. RESULTS: In comparison with Christians, a higher percentage of Muslims responded 'don't know' in questions about the pill's efficacy in regulating menses (p = 0.019), 'yes' concerning the inconvenience of daily uptake (p = 0.032) and the pill's contribution to nausea (p = 0.003), and 'maybe' in the question concerning the pill's contribution to depression and headaches (p < 0.001). A higher percentage of Christians responded 'yes' concerning the pill's contribution to depression and headaches, and 'don't know' concerning the pill's contribution to nausea. There were no significant differences in the responses to the remaining questions, and it was clear that most women believed that use of the pill is correlated with increased risk of cardiovascular disease and cancer. CONCLUSIONS: Muslims appeared more reluctant than Christians to use the pill as a contraceptive method. Christians seemed to be better informed about the pill's phamacological actions and beneficial effects, but both populations were unaware of current information regarding the pill's safety. There is a need to promote information about these topics in Thrace.

The contribution of rapid intraoperative cytology to the improvement of ovarian cancer staging.

OBJECTIVE: The goal of this work was to evaluate the use of intraoperative cytology in the improvement of ovarian cancer staging. METHODS: Fifty-two patients with clinical stage IA-IIB ovarian cancer underwent peritoneal washing (PW) cytology and imprint cytology performed on retroperitoneal lymph node samples, during primary surgical treatment. Cytologic specimens were stained by the May-Grünwald-Giemsa (MGG) and hematoxylin-eosin (HE) techniques. Pertinent histologic sections of the ovarian lesions, cell blocks prepared from PW sediments, and lymph node samples were studied and compared with the cytologic findings. RESULTS: Our study reveals that, when malignant cells are present in the peritoneal cavity, PW cytology has 84.6% sensitivity and 94.7% specificity in detecting them. Imprint cytology performed on lymph node samples presented 94.1% sensitivity and 94.1% specificity in the diagnosis of retroperitoneal metastasis of ovarian cancer. Only 7 patients (13.4%) were upstaged with either cytologic method. PW cytology alone upstaged 6 more patients, while imprint cytology alone upstaged 11 more patients. This corresponds to a total of 17 patients (32.6%) who benefit from the combined performance of both cytologic methods. HE stain presents lower values of sensitivity and specificity compared with MGG. CONCLUSION: Cytologic evaluation of intraperitoneal and retroperitoneal spread of ovarian cancer by use of PW cytology and imprint cytology performed on lymph node samples contributes to the improvement of ovarian cancer staging.