Effects of anti-sclerostin antibody and running on bone remodeling and strength.

Sclerostin antibody (Scl-Ab) represents a promising therapeutic approach to treat patients with osteoporosis. PURPOSE: The aim of this study was to investigate the effects of Scl-Ab, running and a combination of both on bone formation. METHODS: Sixty female Wistar rats, aged 8 months were randomly assigned to five groups (subcutaneous injections performed twice a week): (1) (Sham): sedentary rats + saline, (2) (OVX): ovariectomized rats + saline, (3) (OVX + E): OVX rats + saline + treadmill training (5 times/week, 1 h/day), (4) (OVX + E + S): OVX rats + treadmill training + 5 mg/kg Scl-Ab and (5) (OVX + S): OVX rats + 5 mg/kg Scl-Ab. After 14 weeks, body composition, whole body and femoral BMDs were determined by DXA and serum was collected for analysis of osteocalcin and NTX. Bone microarchitecture was analyzed using µCT and bone strength was assessed at the femur mid-shaft in 3-point bending. RESULTS: Running exercise decreased fat mass as well as the bone resorption marker NTX relative to the non-exercised control groups, effects that were associated with a prevention of the deleterious effects of OVX on whole body and femoral BMDs. Scl-Ab increased the bone formation marker osteocalcin, which resulted in robust increases in BMD and femoral metaphyseal bone volume to levels greater than in the Sham group. OVX + S + E group did not further impact on bone mass relative to the OVX + S group. At the cortical femur diaphysis, Scl-Ab prevented the decreases in bone strength after OVX, while exercise did not affect cortical strength. CONCLUSION: We suggest that while running on a treadmill can prevent some bone loss through a modest antiresorptive effect, it did not contribute to the robust bone-forming effects of Scl-Ab when combined in an estrogen ablation model.

Mesenchymal stem-cell potential in cartilage repair: an update.

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field.

Idiopathic bleeding during the second half of pregnancy as a risk factor for adverse perinatal outcome.

OBJECTIVE: To investigate pregnancy outcome in women suffering from idiopathic vaginal bleeding (IVB) during the second half of pregnancy. METHODS: A comparison between patients admitted to the hospital due to bleeding during the second half of pregnancy and patients without bleeding was performed. Patients lacking prenatal care as well as multiple gestations were excluded from the analysis. Stratified analyses using the Mantel-Haenszel technique and a multiple logistic regression model were performed to control for confounders. RESULTS: During the study period, 173,621 singleton deliveries occurred at our institute. Of these, 2077 (1.19%) were complicated with bleeding upon admission during the second half of pregnancy. After excluding cases with bleeding due to placental abruption, placenta previa, cervical problems, etc., 67 patients were classified as having IVB (0.038%). Independent risk factors associated with IVB, using a backward, stepwise multivariable analysis were oligohydramnios (OR=6.2; 95% CI 3.1-12.7; p < 0.001), premature rupture of membranes (OR=3.4; 95% CI 1.8-6.2; p < 0.001), intrauterine growth restriction (IUGR, OR 5.6; 95% CI 2.5-12.2; p < 0.001), and Jewish ethnicity (OR=1.9; 95% CI 1.0-3.5; p=0.036). These patients subsequently were more likely to deliver preterm (<37 weeks, 56.7% vs. 7.3%; mean gestational age of 33.6+/-5.7 weeks vs. 39.2+/-2.1 weeks; p < 0.001) and by cesarean delivery (CD, 35.8% vs. 12.1%, OR=4.0; 95% CI 2.4-6.6; p < 0.001). Higher rates of low Apgar scores (<7) at 1 and 5 minutes were noted in these patients (OR=10.3; 95% CI 5.9-17.8; p < 0.001 and OR=17.8; 95% CI 7.1-44.5; p < 0.001, respectively). Moreover, perinatal mortality rate among patients admitted due to idiopathic bleeding was significantly higher as compared to patients without bleeding (9.6% vs. 1.2%, OR=8.4; 95% CI 3.3-21.2; p < 0.001). However, when controlling for preterm delivery, using the Mantel-Haenszel technique, the association lost its significance. CONCLUSION: Idiopathic vaginal bleeding during the second half of pregnancy is a risk factor for adverse perinatal outcome, mostly due to its significant association with preterm delivery. Careful surveillance, including fetal monitoring, is suggested in these cases in order to reduce the adverse perinatal outcome.

Early sonographic prenatal diagnosis of seizures.

Fetal seizures are an unusual phenomenon. When diagnosed by ultrasonography, they are frequently associated with malformations and carry a poor prognosis. We describe first trimester seizures in two siblings with arthrogryposis multiplex congenita. In both cases, convulsions appeared before other sonographic signs of the disease. Review of the literature revealed 11 other cases of fetal seizures diagnosed by ultrasound, all later in gestation. Fetal seizures may be the first manifestation of defective neural and motor development. Therefore, in pregnancies at high risk for neuromuscular disease, early sonographic evaluation of fetal motility, in addition to the anatomical survey, is advised.

Cervical length assessment in women with idiopathic polyhydramnios.

OBJECTIVE: The aims of the study were to determine cervical length among patients with polyhydramnios and to assess the relationship between the severity of polyhydramnios, cervical length and gestational age at delivery. PATIENTS AND METHODS: A prospective study was designed including 92 consecutive singleton pregnancies with polyhydramnios between 24 and 40 weeks' gestation. Cervical length was measured using transvaginal sonography. Polyhydramnios was defined when amniotic fluid index (AFI) was equal to or greater than 20 cm. A single sonologist performed all the examinations of the cervical length and the AFI. RESULTS: The median cervical length and AFI were 37.5 (range, 7-52) mm and 28.8 (range, 20-43) cm, respectively. A significant gradual shortening of the cervical length was observed with advancing gestational age (P=0.027). No significant association was found between AFI and cervical length (P=0.24). A cut-off of 15 mm (n=5) was associated with a significantly lower gestational age at delivery (30+/-2.6 weeks vs. 37.2+/-4.2 weeks, respectively, P<0.001). CONCLUSIONS: Women with polyhydramnios have a gradual shortening of cervical length with advancing gestational age. However, this finding is not related to the severity of polyhydramnios.

The preterm parturition syndrome.

The implicit paradigm that has governed the study and clinical management of preterm labour is that term and preterm parturition are the same processes, except for the gestational age at which they occur. Indeed, both share a common pathway composed of uterine contractility, cervical dilatation and activation of the membranes/decidua. This review explores the concept that while term labour results from physiological activation of the components of the common pathway, preterm labour arises from pathological signalling and activation of one or more components of the common pathway of parturition. The term "great obstetrical syndromes" has been coined to reframe the concept of obstetrical disease. Such syndromes are characterised by: (1) multiple aetiology; (2) long preclinical stage; (3) frequent fetal involvement; (4) clinical manifestations that are often adaptive in nature; and (5) gene-environment interactions that may predispose to the syndromes. This article reviews the evidence indicating that the pathological processes implicated in the preterm parturition syndrome include: (1) intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical insufficiency; and (7) hormonal disorders (progesterone related and corticotrophin-releasing factor related). The implications of this conceptual framework for the prevention, diagnosis, and treatment of preterm labour are discussed.

A novel method to improve prenatal diagnosis of abnormal systemic venous connections using three- and four-dimensional ultrasonography and 'inversion mode'.

OBJECTIVE: The precise prenatal diagnosis of abnormal venous connections of the fetal heart is challenging. Anatomical accuracy may be important in determining the best route for postnatal angiography, as well as the prognosis and treatment. This study was designed to determine the value of 'inversion mode', a new three- and four-dimensional (4D) rendering algorithm, in the visualization of the spatial relationships of an interrupted inferior vena cava (IVC) with azygos or hemiazygos vein continuation associated with and without heterotaxic syndromes. METHODS: Heart volumes were acquired using 4D ultrasonography and spatiotemporal image correlation in cases of interrupted IVC with azygos/hemiazygos continuation (n = 3). Volume datasets were rendered using the 'inversion mode' algorithm and abnormal images were compared to those generated from a library of normal fetuses. RESULTS: The 'inversion mode' rendering algorithm allowed the visualization of dilated azygos or hemiazygos veins and their spatial relationships with the descending aorta, the aortic arch, the superior vena cava, and the atria in cases of interrupted IVC with and without heterotaxic syndromes. CONCLUSIONS: The 'inversion mode' algorithm improves prenatal visualization of both dilated azygos and hemiazygos veins, as well as their spatial relationships with the surrounding vascular structures. This has implications for the accurate prenatal diagnosis and management of neonates with abnormal systemic venous connections.

The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the prevalence and clinical significance of amniotic fluid (AF) 'sludge' observed during transvaginal ultrasound examination of the cervix in patients with preterm labor and intact membranes, and in those with uncomplicated pregnancies. METHODS: This retrospective study included patients with preterm labor and intact membranes (n = 84) and those with uncomplicated term pregnancies (n = 298). The outcome variables included the occurrence of documented microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), a composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks. Statistical analysis included Chi-square test, stepwise logistic regression analysis and survival analysis. RESULTS: The prevalence of AF 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. Among patients with preterm labor and intact membranes: (1) cervical length < or = 15 mm was present in 58.3% (49/84) of the patients; (2) the prevalence of MIAC and histological chorioamnionitis was 12.1% (7/58) and 32.9% (25/76), respectively; (3) the rate of spontaneous preterm delivery within 48 h, 7 days, and < 32 weeks and < 35 weeks of gestation was 13.6% (8/59), 28.8% (17/59), 39.5% (17/43) and 50.8% (30/59), respectively; (4) patients with AF 'sludge' had a higher frequency of positive AF cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] than those without AF 'sludge'; (5) a higher proportion of neonates born to patients with AF 'sludge' was admitted to the NICU [64.3% (9/14) vs. 12.9% (8/62), P < 0.01], had a composite neonatal morbidity [36.8% (7/19) vs. 13.8% (9/65), P = 0.04] and died in the perinatal period [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those born to women without 'sludge'; (6) a higher proportion of patients with AF 'sludge' had spontaneous delivery within 48 h [42.9% (6/14) vs. 4.4% (2/45), P = 0.001], within 7 days [71.4% (10/14) vs. 15.6% (7/45), P < 0.001], < 32 weeks [75% (9/12) vs. 25.8% (8/31), P = 0.005] and < 35 weeks [92.9% (13/14) vs. 37.8% (17/45), P < 0.001] than those without AF 'sludge'; and (7) patients with AF 'sludge' had a shorter examination-to-delivery interval than those without AF 'sludge' [AF 'sludge' median, 1 (IQR, 1-5) days vs. no AF 'sludge' median, 33 (IQR, 18-58) days; P < 0.001]. CONCLUSION: The presence of AF 'sludge' in patients with preterm labor and intact membranes is a risk factor for MIAC, histological chorioamnionitis and impending preterm delivery.

Fetal cardiac dysfunction in preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (PROM) is associated with one-third of preterm births. In about 50% of preterm PROM cases, the fetuses will elicit a fetal inflammatory response syndrome (FIRS). FIRS is associated with the impending onset of preterm labor, periventricular leukomalacia, neonatal sepsis, and long-term handicap, including the development of bronchopulmonary dysplasia and cerebral palsy. The fetal myocardium is a potential target organ of proinflammatory cytokines released during FIRS. The objective of this study was to determine whether preterm PROM is associated with functional changes in the fetal heart, as determined by fetal echocardiography. METHODS: A retrospective study was conducted to assess the diastolic function of fetuses with preterm PROM with documented microbial invasion of the amniotic cavity (n = 25), preterm PROM without microbial invasion of the amniotic cavity (n = 42), and fetuses from normal pregnancies (control group = 150). Pregnancies with multiple gestation, fetal distress, fetuses that were small for gestational age, and major congenital anomalies were excluded. Fetal echocardiography studies were performed with two-dimensional ultrasound, color Doppler imaging and pulsed Doppler ultrasound. Non-parametric statistics were used for comparisons. A p value of < 0.05 was considered significant. RESULTS: The prevalence of positive amniotic fluid cultures for micro-organisms in patients with preterm PROM was 35.8% (24/67). Ureaplasma urealyticum was the most frequent isolate, either alone (41.7%; 10/24) or with other micro-organisms (29.2%; 7/24). Fetuses with preterm PROM had a higher delta early diastolic filling/atrial contraction (E/A) peak velocity ratio, a higher delta E/A velocity-time integral (VTI) ratio, a lower delta A peak velocity, a lower delta A VTI, and a lower A VTI/total VTI ratio in the mitral valve compared to those with uncomplicated pregnancies. The delta E/A peak velocity ratio was significantly higher and the delta A VTI significantly lower in fetuses with preterm PROM and microbial invasion of the amniotic cavity than in those with preterm PROM without microbial invasion of the amniotic cavity. CONCLUSIONS: Preterm PROM is associated with changes in fetal cardiac function consistent with increased left ventricular compliance. These observations were also noted in fetuses with microbial invasion of the amniotic cavity. Our findings suggest that fetal cardiac function is altered in preterm PROM and, in particular, in cases with intra-amniotic infection.

Prenatal diagnosis of membranous ventricular septal aneurysms and their association with absence of atrioventricular valve 'offsetting'.

Congenital aneurysm of the membranous portion of the ventricular septum in association with absence of atrioventricular valve 'offsetting' was diagnosed in two fetuses at 29 and 34 weeks. In the first case the fetus had a normal karyotype and no other structural heart defects, whereas in the second case there was a partial deletion of the long arm of chromosome 5 and an absent pulmonary valve syndrome. The association of absence of 'offsetting' with aneurysms of the membranous ventricular septum may represent spontaneous closure of ventricular septal defects initially extended to the inlet.

Broadcasts of wing-fanning vibrations recorded from calling male Ceratitis capitata (Diptera: Tephritidae) increase captures of females in traps.

Female Mediterranean fruit flies, Ceratitis capitata (Wiedemann), from the sterile-male rearing facility in El Pino, Guatemala, were exposed to broadcasts of wing-fanning vibrations recorded from males engaged in calling behavior to investigate the feasibility of developing a female-selective acoustic trap. The recorded signals had frequent amplitude fluctuations and peak frequencies approximately 350 Hz, typical of signals observed in previous studies of Mediterranean fruit fly acoustic behavior. Females did not exhibit long-distance phonotaxis, but remained near a speaker significantly longer when the sounds were broadcast at 103-107 dB than when the speaker was silent. In addition, significantly higher percentages of females were captured by yellow adhesive traps next to a broadcasting speaker than by traps next to a silent mimic. Additional bioassays were conducted with synthetic, 350-Hz tones produced by a thermoacoustic tube as well as with silent mimics of the different sound sources to examine the relative responsiveness of female Mediterranean fruit flies to traps with different acoustic and visual features. The visual attributes of the different sound source assemblies significantly affected capture rates. The range over which the broadcast significantly increased the percentage of female captures was <0.5 m, which may limit the utility of these acoustic cues in large-scale trapping programs. However, the findings of this study do justify further testing of whether optimized short-range acoustic signals could be used to augment longer range pheromonal and visual cues to improve the efficacy of female-selective traps.

Chronic hypertension and the risk for adverse pregnancy outcome after superimposed pre-eclampsia.

OBJECTIVE: To determine the risk factors and pregnancy outcome of patients with chronic hypertension during pregnancy after controlling for superimposed preeclampsia. METHOD: A comparison of all singleton term (>36 weeks) deliveries occurring between 1988 and 1999, with and without chronic hypertension, was performed. Stratified analyses, using the Mantel-Haenszel technique, and a multiple logistic regression model were performed to control for confounders. RESULTS: Chronic hypertension complicated 1.6% (n=1807) of all deliveries included in the study (n=113156). Using a multivariable analysis, the following factors were found to be independently associated with chronic hypertension: maternal age >40 years (OR=3.1; 95% CI 2.7-3.6), diabetes mellitus (OR=3.6; 95% CI 3.3-4.1), recurrent abortions (OR=1.5; 95% CI 1.3-1.8), infertility treatment (OR=2.9; 95% CI 2.3-3.7), and previous cesarean delivery (CD; OR=1.8 CI 1.6-2.0). After adjustment for superimposed preeclampsia, using the Mantel-Haenszel technique, pregnancies complicated with chronic hypertension had higher rates of CD (OR=2.7; 95% CI 2.4-3.0), intra uterine growth restriction (OR=1.7; 95% CI 1.3-2.2), perinatal mortality (OR=1.6; 95% CI 1.01-2.6) and post-partum hemorrhage (OR=2.2; 95% CI 1.4-3.7). CONCLUSION: Chronic hypertension is associated with adverse pregnancy outcome, regardless of superimposed preeclampsia.

Umbilical cord prolapse and perinatal outcomes.

OBJECTIVES: To determine obstetric risk factors and perinatal outcomes of pregnancies complicated by umbilical cord prolapse. METHODS: A population-based study was performed comparing all deliveries complicated by cord prolapse to deliveries without this complication. Statistical analysis was performed using multiple logistic regression models. RESULTS: Prolapse of the umbilical cord complicated 0.4% (n=456) of all deliveries included in the study (n=121,227). Independent risk factors for cord prolapse identified by a backward, stepwise multivariate logistic regression model were: malpresentation (OR=5.1; 95% CI 4.1-6.3), hydramnios (OR=3.0; 95% CI 2.3-3.9), true knot of the umbilical cord (OR=3.0; 95% CI 1.8-5.1), preterm delivery (OR=2.1; 95% CI 1.6-2.8), induction of labor (OR=2.2; 95% CI 1.7-2.8), grandmultiparity (>five deliveries, OR=1.9; 95% CI 1.5-2.3), lack of prenatal care (OR=1.4; 95% CI 1.02-1.8), and male gender (OR=1.3; 95% CI 1.1-1.6). Newborns delivered after umbilical cord prolapse graded lower Apgar scores, less than 7, at 5 min (OR=11.9, 95% CI 7.9-17.9), and had longer hospitalizations (mean 5.4+/-3.5 days vs. 2.9+/-2.1 days; P<0.001). Moreover, higher rates of perinatal mortality were noted in the cord prolapse group vs. the control group (OR=6.4, 95% CI 4.5-9.0). Using a multiple logistic regression model controlling for possible confounders, such as preterm delivery, hydramnios, etc., umbilical cord prolapse was found to be an independent contributing factor to perinatal mortality. CONCLUSIONS: Prolapse of the umbilical cord is an independent risk factor for perinatal mortality.

Treatment of obstetric hemorrhage with recombinant activated factor VII (rFVIIa).

Recombinant activated factor VII (rFVIIa, NovoSeven) was used in three patients with massive obstetric hemorrhage due to placenta previa accreta, rupture of the uterus and pre-eclampsia with HELLP. Administration of the drug markedly decreased the bleeding and enabled control of the hemorrhage. rFVIIa seems to be an adjunctive hemostatic measure for the treatment of severe obstetric hemorrhage.

Anemia during pregnancy and treatment with intravenous iron: review of the literature.

Anemia, the decrease of the hemoglobin concentration with a consequent decrease in the hematocrit level, is a common disorder complicating pregnancies and is mostly due to iron deficiency. The increase of iron requirements, plasma volume, and the poor intake of iron constitute the principal causes of this deficiency. The present review summarizes the current literature regarding anemia during pregnancy and the parenteral iron therapy options.

The reduction of a nitroxide spin label as a probe of human blood antioxidant properties.

The kinetics of reduction of the radical R*, 5-dimethylaminonaphthalene-1-sulfonyl-4-amino-2,2,6,6-tetramethyl-1-piperidine-oxyl by blood and its components were studied using the EPR technique. The results demonstrate that R* is adsorbed to the outer surface of the membrane and does not penetrate into the erythrocytes. A series of control experiments in PBS demonstrate that ascorbate is the only natural reducing agent that reacts with R*. The observed first order rate of disappearance of the nitroxide radical k, is: k(blood) > k(eryth) > k(plasma) and k(blood) approximately = k(eryth) + k(plasma). The results demonstrate that: a. The erythrocytes catalyze the reduction of R* by ascorbate. b. The rate of reduction of the radical is high though it does not penetrate the cells. c. In human erythrocytes there is an efficient electron transfer route through the cell membrane. d. The study points out that R* is a suitable spin label for measuring the reduction kinetics and antioxidant capacity in blood as expressed by reduction by ascorbate.

Placental abruption in term pregnancies: clinical significance and obstetric risk factors.

OBJECTIVE: To determine the incidence, obstetric risk factors and pregnancy outcome of placental abruption at term. METHODS: A comparison of all singleton term deliveries (> or = 37 weeks' gestation) complicated with placental abruption to singleton term deliveries without placental abruption. Multivariate analysis was performed to investigate independent risk factors for placental abruption. RESULTS: Placental abruption complicated 0.3% of all term deliveries (n = 72,995). A multiple logistic regression model with backward elimination found the following factors to be independently associated with the occurrence of placental abruption in term pregnancies: pregnancy-induced hypertension (PIH), intrauterine growth restriction (IUGR), non-vertex presentation, hydramnios and advanced maternal age. Perinatal mortality was significantly higher in pregnancies complicated with placental abruption (OR = 30.0, 95% CI 19.7-45.6; p < 0.001). In order to assess whether the increased risk for perinatal mortality was due to the placental abruption or to its significant association with other risk factors, a multivariate analysis was constructed with perinatal mortality as the outcome variable. Placental abruption (OR = 50.5, 95% CI 32.2-79.1), cord prolapse, small for gestational age and congenital malformations were found to be independent risk factors for perinatal mortality. CONCLUSION: Abruption of the placenta at term was found to be significantly associated with PIH, non-vertex presentation, IUGR, hydramnios and advanced maternal age. Owing to the independent association found between placental abruption and perinatal mortality, these conditions should be carefully evaluated in order to reduce the occurrence of placental abruption.

[Out of hospital deliveries: incidence, obstetrical characteristics and perinatal outcome].

Traditionally, women used to deliver their babies at home. In 1927, in England and Wales, 85% of births took place at home. By 1970 the position was reversed. The move from home to institutional delivery has been accompanied by changes in the institutions themselves and in the type of care provider. There are two kinds of out-of-hospital deliveries: 1. Planned home deliveries--women who decide to deliver in their home with the assistance of midwives or other consultant obstetric facilities. Few cases from this group, however, end up in the hospital; 2. Unplanned home deliveries or delivery en-route to the hospital--when women enter the active phase of labor rapidly, resulting in accidental out-of-hospital deliveries. The study aims to review the available literature and to describe the incidence, obstetrical characteristics and perinatal outcome of out-of-hospital deliveries.