Debra Myers, M.D.

• Assistant Professor
• Department of Internal medicine
• Wayne State University School of Medicine
• Detroit, MI

Most fetal medicine specialists will offer amniocentesis if there is cerebral ventriculomegaly erectile dysfunction injection therapy cost buy zudena 100 mg, a significantly small baby or an enlarged nuchal fold erectile dysfunction under 30 buy online zudena. The process of obtaining consent is not a one-off event erectile dysfunction doctors in orange county buy generic zudena 100 mg, involving interactions with various health professionals including midwives top rated erectile dysfunction pills zudena 100mg without prescription, obstetricians erectile dysfunction causes depression cheap zudena 100 mg, ultrasonographers and family doctors impotence penile rings buy zudena visa. Strategies are required so that the individualized needs of women with physical, cognitive, sensory disability or language barriers should be met from the point of view of counselling for Down syndrome screening. Standards stipulate this written and verbal information must be received by the woman at least 24 h prior to making a screening decision. The information given by healthcare professionals must be impartial and non directive. Women should be aware that the screening test is optional and should not be made to feel their consent is expected by the person offering the test. The discussion must include a definition of the condition being screened for as well as the nature, purpose and limitations of the screening test. This entire process must be documented in the Trusts notes or maternity computer system and Trusts are required to produce a yearly audit against these standards to incorporate in an annual report. The antenatal screening coordinator is required to support the entire programme and ensure that all health professionals in the Trust with a screening role receive an appropriate induction and participate in an education programme which will equip them adequately for their role in offering and performing screening for Down syndrome in pregnancy. They are available as a source of specialist advice, and offer support to health professionals involved in screening. The screening coordinators are equipped to identify any areas requiring development or improvement and by linking with the clinical governance board create an ongoing process of quality assurance. All sonographers performing nuchal translucency scans must be appropriately trained and should provide yearly evidence of image quality. All their measurements are plotted on a distribution and further training is required for any sonographer who has a distribution significantly different from the norm. Ideally, a minimum number of nuchal translucency scans should be performed each year by any one particular practitioner. This governance process allows management of identified risks within the screening programme. There are, however, some pregnancies that are complicated due to maternal or fetal disease that can increase the risk of perinatal morbidity and mortality. The aim of fetal surveillance is to identify these threatened fetuses with the prospect of altering the timing of delivery to prevent the worst outcome, stillbirth. This article looks at the tools available to assess antenatal fetal health in all pregnancies and their ability to identify the at-risk pregnancies that require extra surveillance to improve outcomes. Uterine artery Doppler assessment at 20e24 weeks should be offered in the presence of three or more minor risk factors. Throughout their pregnancy women should be given information that is easy to understand, is accurate, balanced and based on current evidence. This is to allow women to make informed choices about the care they receive throughout pregnancy (Box 1). Introduction the aim of midwives and obstetricians is to identify those pregnancies considered high-risk, due to numerous circumstances (maternal disease, fetal pathology, placental pathology or intrapartum complications), and provide a level of support necessary to take these pregnancies to healthy positive outcomes. The aim for undertaking this monitoring is to reduce perinatal morbidity and mortality and to identify the ideal timing for delivery to achieve the most successful outcome. The vast majority of pregnancies, however, are considered low-risk and result in a healthy term delivery. As a result of this and the fact that pregnancy is a normal physiological process it should be central that any intervention should be beneficial and acceptable to pregnant women. This review looks at the surveillance options available for low-risk pregnancies as well as methods used when a pregnancy is deemed high-risk. This article does not address fetal surveillance during labour or management of established complications like pre-eclampsia or growth restriction. These women should be referred on for further assessment of growth with the use of ultrasound. Although there are concerns that there is inter-operator variability using this technique, its low cost and requirement of minimal time, training and equipment make it a valuable screening method, especially in low-income countries where ultrasound resources are greatly limited. There was no randomized controlled trial evidence comparing population to customized growth charts e evidence was derived from an observational cohort study. Fetal wellbeing cannot accurately be predicted with the use of fetal heart auscultation as it cannot detect subtle variations in beat-to-beat variability or, on a larger scale, fetal accelerations and decelerations which could be demonstrated on a continuous cardiotocograph monitor. These fetuses are appropriately sized in relation to parental body mass index, ethnicity and parity. In contrast, fetuses with growth restriction fail to reach their genetic growth potential due to a tail off in fetal growth. The addition of High-risk pregnancy the aim of assessing the fetus in the antenatal period is to identify those fetuses at-risk of developing complications such as growth restriction and to ultimately reduce the risk of perinatal mortality and morbidity by modifying and individualizing care. It is noted that reduced or no fetal movements can be a sign of imminent fetal death in utero. This is due to chronic fetal hypoxia resulting in reduced fetal movement in an attempt to reduce oxygen consumption. Evidence from meta-analysis suggests formal fetal movement counting using kick charts is not recommended for monitoring in the antenatal period as it failed to show improvement in perinatal outcome. Additionally, failure of the assessment tools may be related to their low positive predictive value: 1250 pregnancies would have to be formally monitored in order to prevent one fetal death in a low-risk pregnancy. However, the perception of reduced fetal movements by the mother should not be ignored but should trigger further less subjective forms of surveillance of fetal wellbeing. Reassuring values for a fetus beyond 26 weeks, over a 20 minute period, include a baseline rate between 110 and 160 beats per minute, a variability between 5 and 25 beats per minute, a greater than 15 beats per minute increase from the baseline for greater than 15 seconds (accelerations), and absence of greater than 15 beats per minute decrease from the baseline for greater than 15 seconds (decelerations). A normal fetal heart rate varies with vagal and sympathetic tone as well as gestational age, whilst hypoxia additionally leads to reduction in the baseline variability, accelerations to be reduced or absent and decelerations may occur. Ultrasound biometry and estimated fetal weight Placental dysfunction results in a reduction in the nutrient supply to the fetus. Whilst the blood supply to the vital organs of the heart and brain are maintained, adaptation occurs with mobilization of glycogen stores from the liver and a reduction in blood flow to , and growth of, non-vital organs like the gut, liver and kidneys. Amniotic fluid volume can also be affected by other factors, such as maternal diabetes, ruptured membranes, structural renal problems or swallowing disorders in the fetus. Ultrasonography to measure the level of fluid around the fetus can be used as a measurement of fetal wellbeing. Although there is poor correlation between these measurements and true amniotic fluid volume, oligohydramnios can be associated with perinatal morbidity and mortality. The predictive value oligohydramnios in isolation (normal uterine artery Doppler and normal growth) for poor outcome is uncertain. There was, however, no difference between methods in terms of the peripartum outcome measures of admission to the neonatal unit, Apgar scores, umbilical artery pH less than 7. The reduced numbers diagnosed with oligohydramnios without change in perinatal morbidity and mortality led the authors to recommend that the single deepest vertical pool should be used as a predictor of antenatal fetal wellbeing, although they also suggest a diagnostic accuracy study of the two methods. Doppler studies the use of Doppler ultrasound technology allows one to assess maternal uterine and fetal circulations. Clinically, this can be expressed as a pulsatility or resistance index based on calculations between systolic and diastolic velocities. There is no value to repeating the uterine artery Doppler results in later pregnancy. With normal placental function, there is forward flow through to the umbilical artery, in both systole and diastole, in a low resistance blood flow system. Sequentially, the patho-physiological consequence is for a raised umbilical Doppler to progressively lead to absent then a reversed diastolic flow. The use of umbilical artery Doppler has been researched in both low- and high-risk pregnancy populations. Observational studies have shown that placental function and outcomes progressively deteriorate as Doppler waveforms evolve from positive to absent to reversed end diastolic flow. Cardiac decompensation and dysfunction, due to hypoxia of the myocardial tissue is characteristic of the end stage of placental insufficiency. This results in venous pulsations in the umbilical vein and reversal of the a-wave in the ductus venosus. This allows optimal timing of delivery, thereby achieving the maximal gestational age without compromising perinatal morbidity and mortality. It is reasonable to repeat umbilical artery Dopplers every 2 weeks if the indices are normal. The ductus venosus should be used to time delivery in those with abnormal umbilical artery Doppler prior to 32 weeks gestation. Observational studies have shown that global reduction in fetal movements and breathing equate to a mean pH of between 7. The disease process is even further advanced when there is additionally a reduction in fetal tone. Customised versus population-based growth charts as a screening tool for detecting small for gestational age infants in low-risk pregnant women. Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus. Computerised fetal heart rate analysis, Doppler ultrasound and biophysical profile score in the prediction of acid-base status of growth restricted fetuses. Practice points C Conclusion Assessment of risk factors for abnormal fetal growth should take place early in the first trimester to ensure appropriate levels of monitoring and surveillance are instituted at appropriate times in the pregnancy. Each pregnancy requires its own individual plan with a possibility of increasing surveillance should the clinical situation change. In high-risk pregnancies, Doppler is used both as a predictor of fetal outcome, with uterine artery Doppler, and as surveillance, with multiple fetal vessel Doppler measurements to predict progressive deterioration in fetal pathology. There are currently no forms of antenatal fetal monitoring that can accurately predict acute events like fetomaternal haemorrhage, cord accident or placental abruption. Arterial and venous Doppler in the diagnosis and management of early onset fetal growth restriction. Women with three or more minor risk factors should be offered uterine artery Doppler assessment at 20e24 weeks and abnormal values should result in serial ultrasound measurements for growth and wellbeing. Normal values should have a single third trimester assessment of fetal size and wellbeing. Reduction in fetal movements reported should prompt further standardized assessments of fetal wellbeing. In high-risk fetuses the use of umbilical artery Doppler reduces perinatal mortality, morbidity, antenatal admissions, induction of labour and caesarean section. Serial measurement of multiple vessel Doppler studies in at-risk pregnancies should be used when there is proven fetal compromise. The strongest predictors of stillbirth are umbilical venous pulsations and reversal of the a-wave in the ductus venosus. The diagnostic and therapeutic role of ultrasound in obstetrics Nirmala Chandrasekaran Basky Thilaganathan Elective use of ultrasound Dating of pregnancy Accurate pregnancy dating is vital in order to improve the performance of Down syndrome screening and to reduce the need for induction of labour after 41 weeks. Last menstrual period estimates of the duration of gestation are subject to both random error and a systematic tendency to overstate the duration of gestation, most likely because of delayed ovulation. Crown rump length is an accurate predictor of gestational age although an average of biparietal diameter, femur length and abdominal circumference has shown comparable accuracy. Inaccurate dating can lead on to overestimate of the maternal risks and result in unnecessary maternal anxiety and invasive testing. A recent Cochrane Review concluded that a policy of labour induction after 41 completed weeks compared to awaiting spontaneous labour is associated with fewer perinatal deaths. Routine early pregnancy scanning will improve the accuracy of pregnancy dating and thereby affect the number of pregnancies undergoing induction for post-maturity. Multiple pregnancies the perinatal mortality rate in twins is six times higher than in singleton pregnancies. The main reason for the increased mortality is due to the pre-maturity related complications which are 3e4 times higher in the monochorionic twins than the dichorionic twins. A reduction in these losses can only be achieved by the accurate identification of chorionicity and adapting adequate surveillance for these fetuses. Chorionicity can be determined by the identification of fetal sex, number of placentas and the characteristic of the separating membrane. More than the fetal sex and the placentae, the intertwin membrane helps in establishing the chorionicity accurately. This comprises the amniotic and chorionic membranes surrounding each fetus separated by some placental tissue. On the other hand, the monochorionic pregnancies have a "T" sign which comprises of the fused amniotic membrane surrounding each fetus inserting into a shared placenta. New developments in the field of screening for pregnancy disorders have led to changes in the clinical application of ultrasound in the care of women with normal and complicated pregnancies. At the recommended intensities for obstetric examination, ultrasound is safe, without adverse effects on mother, fetus or operator. This review highlights the validated uses of ultrasound in obstetrics, such as pregnancy dating, screening for aneuploidy, diagnosis of fetal abnormality, placental localization, diagnosis of chorionicity in multiple pregnancy, assessment of fetal growth and well-being and fetal therapy. Knowledge of the evidence base for the role of ultrasound will result in effective and appropriately timed interventions in pathological pregnancies. This, together with new developments in the field of screening for pregnancy disorders, has led to a change in the clinical application of ultrasound in the care of pregnant women. Techniques such as pulsed wave and colour Doppler imaging play an important role in screening for poor placentation and its consequences of pre-eclampsia, intrauterine growth restriction and perinatal death. It has helped to distinguish normal from complicated pregnancy and decide on the subsequent management. In order that the biometric measurements from the longitudinal growth scans are consistently allocated to the same twin, the twins should be labelled properly during the first trimester.

Other constituents include intestinal epithelial cells erectile dysfunction pills cialis order zudena online now, squamous cells erectile dysfunction statistics age order on line zudena, lanugo erectile dysfunction pills canada buy cheapest zudena, amniotic fluid fda approved erectile dysfunction drugs discount zudena 100 mg with visa, bile acids and salts (giving the characteristic green colour) erectile dysfunction viagra not working buy generic zudena on line, phospholipase A2 impotence treatment drugs generic zudena 100mg line, interleukin-8, mucus glycoproteins, lipids and proteases. The main theories of meconium passage into amniotic fluid are physiological fetal gastrointestinal maturity or alternatively, a pathological process due to fetal stress such as hypoxia or infection. Motilin, an intestinal polypeptide which stimulates contraction of intestinal muscle, is found in higher concentrations in post-term than pre-term fetal gastrointestinal tracts. Furthermore, intestinal parasympathetic innervation and myelination also increase in later gestations, implying that the increasing incidence may reflect the maturation of peristalsis in the fetal intestine. Conversely, in animal studies, term rabbits failed to pass meconium during a hypoxic insult, calling into question, whether this mechanism is a major cause for meconium passage in a hypoxic human fetus. Studies suggest that in utero, hypoxia and acidosis leads to vagally mediated increase in gastrointestinal peristalsis and relaxation of anal sphincter leading to meconium passage. Intrapartum management Due to the mechanisms mentioned above, meconium passage may have different clinical significance at different gestations. Meconium in the term fetus As the fetal gut matures, meconium moves closer to the distal colon and rectum. Therefore, at term there is a close proximity between the meconium and the anal sphincter. For this reason, the amount of fetal stress required to initiate the release of meconium may be trivial and unsustained, such as occurs with cord compression during normal labour. However, in the, absence of the stress of labour, meconium may be more significant. However, when fetal heart rate abnormalities are present, the passage of meconium is associated with a lower umbilical artery pH compared to those with clear amniotic fluid. This could potentially be explained either Grading of meconium For many years attempts have been made to correlate increased meconium thickness with a worse perinatal outcome, but due to the subjectivity of assessing meconium thickness, it makes it very difficult to compare studies with any scientific rigour. However, there does appear to be a significant linear association between meconium thickness and abnormal fetal heart rate patterns during labour, low Apgar scores and risk for caesarean section delivery. There also appears to be a higher risk of neonatal intensive care admission in pregnancies with thick meconium as compared to those with clear amniotic fluid, suggesting that thick meconium, not thin, is associated with an increased risk for perinatal complications during labour and delivery. A system of measuring quantitative meconium concentrations using a "meconiumcrit" (percentage by volume of the solid component of meconium) was proposed in the 1990s, but this has not been adopted clinically, as a study investigating the value of measuring meconiumcrit showed no significant correlation with umbilical artery pH or Apgar score and no clinical benefit. More objective intrapartum measures have been used to assess whether meconium alone can signify fetal distress. This suggests that meconium passage, in the absence of other signs of fetal distress, is not a sign of hypoxia and therefore, is not an indication for fetal blood sampling. Furthermore, meconium-stained amniotic fluid, in the absence of fetal heart rate abnormalities, is associated with reduced Apgar scores and an increased perinatal morbidity and mortality, likely due to meconium aspiration following birth of an otherwise healthy fetus. The early detection and management of fetal hypoxia are important in minimizing the risk from meconium staining of the amniotic fluid. Meconium reduces the antibacterial activity of the amniotic fluid thereby increasing risk of neonatal sepsis. Meconium aspiration syndrome describes a wide spectrum of respiratory disease, ranging from mild respiratory distress to severe disease and death despite mechanical ventilation and can occur if meconium particles are aspirated into the lungs of an infant prior to , during or immediately after birth. Prior to the late 1970s it was thought that aspiration of amniotic fluid and meconium only occurred during the first few breaths after delivery, however, meconium has been found, distally as far as the alveoli in stillborn infants. Further to this, studies with radio-opaque contrast and Cr51 labelled erythrocytes injected into amniotic fluid have demonstrated that amniotic fluid enters the fetal lungs in the non-asphyxiated human fetus, suggesting that meconium aspiration occurs in utero. Animal studies have also shown that intrauterine gasping, resulting in greater aspiration of meconium, occurs in fetuses exposed to hypoxia, implying that fetal distress is a risk factor for development of meconium aspiration syndrome. Currently, there is no way to distinguish those who develop meconium aspiration from intrauterine gasping and those who develop it by inhalation at birth. Pathophysiology the mechanism by which meconium induces this syndrome is multifactorial and complex. Airway obstruction is usually the initial problem encountered by the neonate with meconium aspiration syndrome, although complete obstruction is unusual. Amniocenteses conducted on women presenting with pre-term labour with intact membranes have shown a significantly increased rate of positive amniotic fluid microbial cultures when meconium liquor is present and these women are more likely to deliver pre-term, suggesting that meconium passage is a risk factor for microbial invasion, chorioamnionitis and pre-term delivery. Small airway obstruction is followed by partial alveolar collapse and ventilationperfusion mismatch. Complete airway obstruction of smaller airways with meconium causes air to be absorbed and results in atelectasis. Pneumonitis may develop due to the direct toxic effect of meconium contents and the infiltration of a large number of polymorphonuclear leucocytes and macrophages into the airways and lung parenchyma mediating an intense inflammatory response resulting in direct tissue injury. This inflammatory response is mediated by chemotactic cytokines present in meconium which lead to high levels of vasoactive mediators (leukotrienes, prostaglandins) resulting in pulmonary vasoconstriction. Surfactant inactivation Meconium interferes with the surface tension lowering capacity of surfactant leading to decreased lung compliance and oxygenation. All these mechanisms result in hypoxia, acidosis and hypercarbia, resulting in pulmonary vasoconstriction. If persistent, pulmonary hypertension may develop, a common finding in fatal meconium aspiration syndrome. However, this was repeatedly challenged and more recent evidence supports a more liberal approach, depending on the neonatal condition at birth and the degree of meconium staining of the amniotic fluid. Oropharyngeal and nasopharyngeal suctioning prior to birth of the shoulders, once almost universally accepted, has more recently been shown to have no effect on the incidence of meconium aspiration syndrome, the need for mechanical ventilation or duration of hospital stay when compared to not suctioning. Prenatal suctioning could be dangerous with potential risks associated such as apneas, vagal reflex bradycardia, delay in resuscitation and damage of the palate or pharynx. Additionally, a vigorous baby can make visualization of the vocal cords difficult, thereby, potentially increasing the risk of oesophageal or tracheal injury. Neonatal care Most vigorous babies born through thick meconium-stained amniotic fluid do not require any intervention besides being monitored for signs of respiratory distress, which if occurs generally develops within 12 hours of birth. The most common bacterial isolates are Ureaplasma urealyticum, Escherichia coli, Candida albicans, Streptococci and Listeria monocytogenes. In practice, however, most of these infants will receive antibiotics in the first few days of life before the diagnosis of pneumonia can be ruled out. Prevention of meconium aspiration syndrome Many cases of meconium aspiration syndrome can be prevented by assessment of risk factors, continuous fetal monitoring and appropriate removal of meconium from the pharynx and trachea. However, although airway suctioning is thought to reduce the incidence of meconium aspiration it does not eliminate the risks entirely. Therefore, several other, methods have been proposed to reduce the perinatal mortality and morbidity caused by meconium-stained amniotic fluid. Amnioinfusion Amnioinfusion has been proposed as one method of reducing the risk of meconium aspiration syndrome. It involves infusing normal saline transcervically through a catheter into the uterine cavity, thereby diluting any meconium present and reducing its mechanical and inflammatory effects. Firstly, by preventing or relieving umbilical cord compression during labour, thereby reducing the risk of fetal hypoxia and meconium passage. Complications of amnioinfusion include uterine over-distension and hypertonia, uterine scar rupture, fetal heart rate abnormality, umbilical cord prolapsed and chorioamnionitis. Other potential methods There is no evidence to support the use of maternal narcotics to reduce the incidence of fetal gasping. An assessment of the use of meconium alone as an indication for fetal blood sampling. Maternal and fetal characteristics associated with meconium-stained amniotic fluid. Antibiotics for meconium-stained amniotic fluid in labour for preventing, neonatal sepsis (protocol). Interrelationships among abnormal cardiotocograms in labor, meconium staining of the amniotic fluid, arterial cord blood pH, and Apgar scores. Induction of labor versus expectant management for post-date pregnancy: is there sufficient evidence for a change in clinical practice? Practice points C Conclusion the management of intrauterine meconium passage has generated considerable controversy. Its exact relationship with fetal distress is complex, dependent on several factors including fetal gestation and heart rate abnormalities and is not completely understood. Meconium passage continues to be a common problem and meconium aspiration syndrome is associated with many cases of neonatal respiratory distress, neurological complications and death. Those at greatest risk are those with intrauterine hypoxia, those born with thick meconium and those whose fetal vigour is depressed at birth. Other presentations (which are classified as malpresentations) include breech, face, brow, shoulder and compound presentation. It is usually a prominent bony landmark at the circumference of the presenting part. For a brow presentation the denominator is not fixed and either the sinciput (area of anterior fontanelle) or occiput can be used. Position e refers to the relationship of the denominator to the fixed points on the maternal pelvis such as pubic symphysis, iliopectineal eminence, sacroiliac joints and sacrum. For vertex presentations, the occiput can occupy following positions in labour e occipitoanterior, occipitotransverse or occipitoposterior. Attitude e refers to the degree of flexion or extension of the fetal head with respect to the trunk. As labour advances, with progressive descent and flexion, the occiput rotates to an anterior position once it reaches the pelvic floor. With further uterine contractions and descent, the head is born by extension of the fetal neck followed by restitution. The head then undergoes external rotation as the shoulders continue their internal rotation to come to lie in the sagittal plane for delivery. If the fetal head is not well flexed, the presenting diameters to the pelvis are larger and this causes malpositions or malpresentations. With vertex presentation, the vast majority of women progress well in labour and have spontaneous vaginal delivery. Any presentations other than vertex can lead to difficulties in labour and hence are called as malpresentations. Malpresentations of fetal head occur due to extension of the fetal head causing brow or face to present in labour. Malpositions of fetal head result when the occiput persists in a lateral or posterior position. Malpresentations and malpositions of fetal head are usually diagnosed in labour and are associated with difficult labour and increased risk of operative intervention. Regular systematic clinical examinations to monitor progress of labour and fetal wellbeing are necessary once the diagnosis is confirmed. Although vaginal delivery is possible in many cases, Caesarean section becomes necessary when the malposition or malpresentation persists and labour fails to progress. As labour advances, progressive flexion and descent of fetal head causes the occiput to rotate anteriorly when the head reaches the pelvic floor. When this sequence of changes in the position of fetal head is altered, a malposition or malpresentation occurs. As women chose to have fewer babies, the incidence of malpresentations has fallen in modern times as many of them are associated with high parity. Most of the malpositions or malpresentations of fetal head are diagnosed in labour and while in many cases vaginal delivery is possible, they are associated with difficult labour and increased operative interventions with attendant risks to both the mother and the baby. Fetal head presentations and positions e definitions and mechanisms of labour the term presentation refers to the part of the fetus which is presenting to the pelvic inlet. It can also be defined as the part of Aetiology of malpresentations and malpositions of fetal head the three Ps of normal labour e Power (Uterine activity), Passage (Maternal pelvis and soft tissues) and Passenger (Position and size of fetal head) all play an important role in success of vaginal delivery. Defects in the power e Pendulous abdomen with lax abdominal muscles, weak uterine contractions. Defects in the passage e Contracted pelvis, android pelvis, pelvic tumours, uterine anomalies, placenta praevia. Defects in the passenger e Preterm fetus, intrauterine fetal death, macrosomia, fetal tumours, multiple pregnancy, congenital anomalies, polyhydramnios, cord around the neck. Clinical presentation and diagnosis A thorough and systematic clinical examination is important for diagnosis and further management of fetal head malpositions or malpresentations. Abdominal examination e Signs suggestive of malpresentations include a pendulous abdomen and non-engagement of the presenting part at term in a primigravida. Premature or early rupture of membranes in labour and delay in the descent of the presenting part during labour are notable. Periodic abdominal examination should be performed in labour to assess descent and position of fetal head. While the descent may be assessed by fifths of the fetal head palpable above symphysis pubis, the relative positions of sinciput and occiput may suggest the attitude of the fetal head. Vaginal examination e Vaginal examination often confirms the findings of malposition or malpresentation. When performing a systematic vaginal examination, station of the fetal head should be identified in cm above or below the ischial spines. Placement of sutures and fontanelles should be confirmed by sweeping the fingers across the fetal head. The inverted Y shaped suture lines or overlapping of parietal bones over the occipital bones in labour helps to identify the posterior fontanelle. Anterior fontanelle is felt as a soft diamond shaped depression at junction of four bones. If the anterior fontanelle is felt easily near the centre of the pelvis it indicates the possibility of a deflexed head. If the amount of caput makes examination difficult, it may be possible to feel the fetal ear anteriorly. Care should be taken to feel the pinna and the canal, as the ear can be folded and give a false impression of its position. Also, since the ear is just below the biparietal diameter, it can aid in judging the descent of the head. Anterior asynclitism, in which the anterior parietal bone is more easily felt and the sagittal suture is further back in the transverse plane, is normal.

This promising strategy offers the potential to prevent not only allograft rejection but xenograft rejection as well erectile dysfunction nutritional treatment generic 100 mg zudena otc. In addition to the successful creation of the -1 erectile dysfunction vyvanse purchase zudena with american express,3galactosyltransferase knockout pigs erectile dysfunction doctors northern virginia buy generic zudena on line, several groups have successfully introduced genes that encode decayaccelerating factor erectile dysfunction treatment seattle generic zudena 100mg with visa, which downregulates the complement activation erectile dysfunction solutions discount 100 mg zudena amex, into fertilized pig oocytes impotence drugs cheap zudena amex, thereby producing xenoorgans that have prolonged survival in baboons. Whether or not xenotransplantation will become a clinical reality will largely depend on the ability to genetically engineer a more immunologically inert organ. Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients. Multiparameter immune profiling of operational tolerance in liver transplantation. Comparison of transcriptional and blood cell-phenotypic markers between operationally tolerant liver and kidney recipients. Interleukin-10-1082G/A polymorphism and acute liver graft rejection: a meta-analysis. Mannose-binding lectin and ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. A seven-gene signature (cirrhosis risk score) predicts liver fibrosis progression in patients with initially mild chronic hepatitis C. Role of a cirrhosis risk score for the early prediction of fibrosis progression in hepatitis C patients with minimal liver disease. A 7-gene signature of the recipient predicts the progression of fibrosis after liver transplantation for hepatitis C virus infection. Gene expression profiling of acute liver stress during living donor liver transplantation. Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation. Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts. All this accumulated genomic information will hopefully one day allow clinicians to develop novel therapeutics, make diagnoses earlier and less invasively, and tailor therapies to patients instead of the one-size-fits-all approach seen today. This is being seen more and more in the field of oncology, and the transplant field is not that far off. In addition, there are fields of genetics that the transplant field is just beginning to really embrace-for instance, epigenetics. These processes have been shown to regulate T-cell response and B-cell development and play a role in ischemia-reperfusion syndrome. As the importance of the epigenome is further realized, the potential impact on liver transplantation could be great. Impact of human leukocyte antigen mismatching on outcomes of liver transplantation: a metaanalysis. Human leukocyte antigen crossmatch testing is important for liver retransplantation. Molecular signatures of urinary cells distinguish acute rejection of renal allografts from urinary tract infection. Nagaraj N, Mann M, Quantitative analysis of the intra- and interindividual variability of the normal urinary proteome. Global gene expression profiles of ischemic preconditioning in deceased donor liver transplantation. Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives. Besides offering a plentiful supply of livers, xenotransplantation might offer a transplant inured to hepatitis C. Xenogeneic livers can also be used for extracorporeal "xenoperfusion," for devices containing xenogeneic hepatocytes, auxiliary liver transplants, bridge liver transplants, and hepatocyte transplants. The hurdles to xenotransplantation of the liver include the immune response of the recipient against the graft, incompatibility of the graft with complex physiological and biochemical systems of the recipient, and the possibility of transferring infectious agents from the graft to the recipient. Recent progress in characterizing and overcoming these hurdles has encouraged some optimism regarding the ultimate application of xenotransplantation for the treatment of human disease. Allogeneic organ transplantation is the preferred therapy for patients with irreversible functional failure of such organs as the liver, kidneys, heart, and lungs. Although the need for liver transplantation will decrease with improvements in the care of patients with liver disease, particularly hepatitis C, a more comprehensive solution to the problem will require the development of artificial organs or the development of another source of organs for transplantation. The use of animals as a source of organs and tissues for transplantation, called xenotransplantation, is thus a way that transplantation can realize its full potential as an approach to human disease. In this chapter we review the various ways that xenogeneic livers and hepatocytes might be applied for the treatment of hepatic disease. However, xenotransplantation also offers 1420 103 Liver and Hepatocyte XenotranspLantation 1421 a potential way to avoid recurrence of hepatitis B or hepatitis C in a transplant, because these viruses evidently do not infect animal livers. These defects are now treated by orthotopic liver allotransplantation,4 even though the structure and most functions of the native liver are intact. Instead, these defects might be treated by hepatocyte transplantation, leaving the native liver in place to provide all other functions. The transgenic animal thus produced might express the gene product, which can be delivered by transplanting xenogeneic cells (or organs). Such a transfer, called cloning, can be used to produce a line of animals with known changes in genetic material,10-12 including expression of transgenes. Those cells or organs might then be transplanted as a means of gaining expression of the gene. The potential applications of xenogeneic livers are discussed briefly in the following sections. Orthotopic Liver Transplantation Orthotopic allotransplantation of the liver is the most effective treatment for hepatic failure. The indications for orthotopic liver transplantation include acute and chronic liver failure, metabolic liver diseases, and unresectable malignant tumors. However, additional indications might include temporary transplantation as a bridge for certain patients awaiting a human liver allograft and as a transplant that would avert reinfection by hepatitis viruses. The chimpanzee-tohuman xenografts functioned for only 1 to 9 days, probably limited mainly by the medical and immunosuppressive therapeutics of that era rather than by the biology of the graft. Two patients with hepatic failure caused by hepatitis B, who received liver xenografts from baboons, functioned for 26 days and 70 days without evidence of reinfection by hepatitis virus. In the early 1960s Reemtsma et al13 transplanted a series of chimpanzee kidneys into patients with renal failure, and in the early 1990s Starzl et al14 transplanted baboon livers into two patients with liver failure. The renal and liver xenografts maintained the survival of patients for up to 9 months. However, nonhuman primates have not been used recently as a source of organs for transplantation because they are available in small number, their size is small, and they could transmit lethal infectious agents. Also, current technology for genetic manipulation would be difficult to undertake in primates and might provoke social opposition. Because of these problems, most investigators today focus on using lower animals, particularly pigs, as a source of organs and tissues for xenotransplantation. Pigs are available in sufficient quantities, and their anatomy and physiology are similar to those of humans. Although the tissue of pigs might transmit some infectious agents, none of these agents poses risks comparable to agents of nonhuman primates. The porcine livers produced albumin, and the porcine coagulation factors rendered coagulation assays at normal values. However, all of the baboons died from uncontrolled bleeding caused by consumptive coagulopathy. Auxiliary transplantation leaves the native liver intact in case of graft failure or spontaneous recovery or for future gene therapy. Auxiliary allografts are not often performed in part because human livers are scarce. Seven auxiliary liver xenotransplants have been performed since 1969 (see Table 103-1). The graft functioned for 24 hours, improving clearance of bilirubin and alkaline phosphatase. Makowka et al30 implanted a porcine liver as an auxiliary graft into a patient with fulminant decompensation of autoimmune hepatitis. Although the porcine xenograft functioned, the patient died from neurological complications 34 hours later. These clinical experiences demonstrate that a pig liver can potentially support patients who suffer from acute liver failure. Auxiliary transplantation of the xenogeneic livers might provide an early step in evaluating the feasibility of clinical xenotransplantation. Another potential limitation is that the anatomical positioning of the cells may not permit optimum secretion of bile. However, recent reports on intrasplenic administration of rat and porcine hepatocytes to reverse chronic liver failure in rats would suggest that this type of transplant could be used for short periods of time to enhance survival. Another important advantage of hepatocyte xenotransplantation is that animal sources could be genetically engineered to express needed enzymes or receptors at high levels. Another advantage is that the immune hurdles to hepatocyte xenotransplantation are less than those to whole-liver transplantation, and a further decrease in such hurdles might be achieved by encapsulation of the cells. Still another advantage may be the opportunity to use fetal cells, were such cells to be needed. Possible applications of hepatocyte xenotransplantation have been explored in experimental models. Gunsalus et al7 showed that porcine hepatocytes introduced into the livers of Watanabe rabbits, which have a genetic defect in low-density lipoprotein receptors causing severe hypercholesterolemia, bring about a substantial lowering of blood cholesterol levels. However, one limitation of hepatocyte xenotransplantation may be the incompatibility of secreted donor proteins with proteins of the recipient,46 which will be discussed later. Ex Vivo Perfusion and Hepatic Assist Devices the perfusion of blood through intact livers or through hepatic assist devices have gained attention as potential approaches to treatment of fulminant hepatic failure and exacerbations of chronic liver disease. Although the use of such procedures is not transplantation, the indications, limitations, and risks of such treatments have a bearing on transplantation, and therefore brief consideration here is warranted. Perfusion of intact livers has been carried out for decades with only limited success47; however, advances in perfusion technologies, including the ability to oxygenate the perfused blood, have allowed the procedure to be applied with lower risk and perhaps greater efficacy. Components of the circuitry, including membranes, filters, tubings, and so on, may activate leukocytes, leading to cytokine release. Function of the perfused organs may be limited by inflammatory and immune reactions. Hepatocyte Transplantation Pigs have also been envisioned as a source of isolated hepatocytes for transplantation. The rationale and early application of allogeneic hepatocyte transplants have been discussed. One especially compelling indication for hepatocyte transplants might be in the treatment of metabolic diseases of the liver. In this case the structure and most functions of the native hepatic parenchyma are normal; the hepatocytes are needed for only limited purposes. The main limitation of hepatocyte transplantation is finding a source of the large number of hepatocytes needed for the procedure. Allogeneic hepatocytes might be obtained from donors who are unsuitable for providing whole-liver transplants. At best, function in the new environment may not be optimal until a period of days has 103 Liver and Hepatocyte XenotranspLantation 1423 An appealing alternative to the use of intact livers is the perfusion of a device containing hepatocytes encased in permeable membrane. A number of such devices have been described, among them being a porcine hepatocytebased "bioartificial liver. Controlled trials using bioartificial livers containing porcine hepatocytes have not revealed definitive improvement in survival of treated patients over conventional intensive care. These hurdles include the immunological response of the recipient against the liver or liver cells, leading to the destruction of foreign cells, the inherent limitation of the xenogeneic liver or the device to restore the physiology in the treated patient, and the possibility of transferring infectious agents from the perfused liver or device to the treated patient and potentially beyond. In the following sections we describe the potential applications of xenotransplantation for the treatment of liver disease and the factors that stand as a barrier to this and other related types of therapy. To a large extent the nature and severity of these hurdles depend on the type of transplant used. Because whole-organ transplants are carried out by primary anastomosis of donor and recipient blood vessels, the vascular system consists entirely of donor blood vessels. These responses constitute a severe barrier to xenotransplantation and will be discussed in detail later. On the other hand, whole-organ xenografts have the advantage of providing their own microenvironment. The hepatocytes are situated in proper orientation and in opposition to appropriate extracellular matrix. Thus an intact organ can function nearly immediately upon transplantation and is not constrained by incompatibilities between parenchymal cells and the microenvironment. Grafts of isolated cells, such as hepatocytes, derive their vascular supply and microenvironment from the recipient. The recipient blood vessels, particularly the endothelial lining of blood vessels, pose a barrier between the immune system of the recipient and the transplanted cells. A, Organ transplantation between unmodified disparate species leads to hyperacute rejection. If hyperacute rejection is averted by depletion of xenoreactive natural antibodies or inhibition of the complement system, the xenograft may be subject to acute vascular rejection, or "accommodation" may occur.

These myomas are located beneath the endometrium and can distort the uterine cavity erectile dysfunction drugs bayer discount zudena 100mg without a prescription. The distorted overlying endometrium may not respond appropriately to the normal hormonal fluctuations erectile dysfunction statistics uk generic 100mg zudena otc, resulting in unpredictable erectile dysfunction medicine in pakistan cheap zudena 100 mg on-line, often intermenstrual erectile dysfunction killing me order 100 mg zudena visa, bleeding erectile dysfunction 20 years old order zudena canada. Abnormal vaginal bleeding is the most common symptom of a submucosal myoma and can result in anemia erectile dysfunction news cheap zudena 100mg with mastercard. Menorrhagia is defined as heavy menses and metrorrhagia is defined as irregular bleeding in between menses. Menometrorrhagia consists of both heavy menses and bleeding in between the menses. As they grow they distort the external contour of the uterus causing the firm, nontender asymmetry. Depending on their location they can put pressure on the bladder, rectum or ureters. If they are pedunculated, attached to the uterus by a stalk, they can become parasitic fibroids. They break away from the uterus and receive their blood supply from another abdominal organ (such as the omentum or the mesentery of the intestine). Estrogen receptors are increased in leiomyomas resulting in rapid enlargement during times of high estrogen levels, such as pregnancy. During times of rapid growth, myomas may outgrow their blood supply, resulting in ischemic degeneration of a fibroid. Common degenerations that are seen include hyaline, calcific, and red degeneration. The latter, also known as carneous degeneration, can cause such extreme, acute pain that the patient requires hospitalization and narcotics. When estrogen levels fall, with estrogen receptors no longer stimulated, leiomyomas will typically decrease in size. In most cases the diagnosis is made clinically by identifying an enlarged, asymmetric, nontender uterus in the absence of pregnancy. Traditional abdominal or vaginal ultrasound can image large intramural or subserosal myomas. Submucosal myomas may be identified by visualizing them directly with hysteroscopy. Most leiomyomas can be managed conservatively and followed expectantly with regular pelvic examinations. However, once the leuprolide (Lupron) is terminated, there will be a regrowth of the fibroid within 6 months. If a myomectomy is done, a decrease in size will be associated with a decrease in blood loss, and if a hysterectomy is planned, then perhaps a vaginal instead of an abdominal hysterectomy can be performed. This is a surgical procedure performed if the patient desires to maintain fertility. The uterus is incised and the myoma removed through either a laparoscopic or laparotomy approach. If the myomectomy incision entered the endometrial cavity, delivery of any subsequent pregnancy should be by cesarean section because of increased risk of scar rupture in labor. This is an invasive radiology procedure in which a catheter is placed into the vessels supplying the myoma. If the patient has completed her childbearing, definitive therapy is an abdominal or vaginal hysterectomy. Ectopic endometrial glands and stroma are located within the myometrium of the uterine wall. The lesion is known as an adenomyoma if the involvement is focal, surrounded by a pseudocapsule. In most cases the diagnosis is made clinically by identifying an enlarged, symmetric, tender uterus in the absence of pregnancy. The only definitive diagnosis is by histologic confirmation of the surgically excised tissue. Differential Diagnosis for Enlarged Non-pregnant Uterus Leiomyoma Asymmetric Firm Nontender Adenomyosis Symmetric Soft Tender Symptoms. She was diagnosed with type 2 diabetes 20 years ago and was treated with oral hypoglycemic agents. She has chronic hypertension, for which she is treated with oral antihypertensives. Physical examination is normal with a normal-sized uterus and no vulvar, vaginal, or cervical lesions. A patient is considered to be in menopause after 3 continuous months of cessation of menses and elevated gonadotropins. The differential diagnosis of postmenopausal bleeding includes endometrial carcinoma, vaginal or endometrial atrophy, and postmenopausal hormonal replacement therapy. Although the most common cause of postmenopausal bleeding is vaginal or endometrial atrophy, the most important diagnosis to rule out is endometrial carcinoma. The mediating factor for most endometrial carcinomas appears to be unopposed estrogen. This results from excessive hyperstimulation of the endometrium without the stabilizing effect of progesterone. This office procedure has historically been the initial diagnostic test for postmenopausal bleeding, due its high sensitivity, low complication rate, and low cost. It is ideal for global lesions but not very sensitive for diagnosing localized structural lesions such as polyps or submucus leiomyomas. This is an acceptable alternative initial test for non-persistent minimal bleeding in women who are not on hormone replacement. A thicker endometrial stripe warrants further assessment with an endometrial sampling. This procedure allows direct visualization of the endocervical canal and endometrial cavity. Endocervical or endometrial polyps, or submucus leiomyomas, can be removed at the time of the hysteroscopy. Spread limited to the uterus (most common stage at diagnosis) Limited to the endometrium or invasion less than half of myometrium Invasion more than half of myometrium Extension to the cervix but not outside the uterus Spread adjacent to the uterus Invades serosa or adnexa or positive cytology Invasion of vagina Invasion of pelvic or para-aortic nodes Spread further from the uterus Involves bladder or rectum Distant metastasis 184 Chapter 4 l Disorders of the Cervix and Uterus Management. If the endometrial histology sampling reveals atrophy and no evidence of cancer, it can be assumed the patient is bleeding from atrophy and can be treated with hormone replacement therapy. With hormone replacement therapy, estrogen and progesterone should be given to the patient. If the endometrial sampling reveals adenocarcinoma, the patient should be treated surgically. An evaluation of the postoperative pathology report will classify patients into poor or good prognosis category. Medical treatment is used for metastatic disease and involves progestins and cytotoxic agents. On pelvic examination, a 6-cm mobile, smooth, soft, left adnexal mass is palpable. An endovaginal pelvic ultrasound shows a 6-cm, round, fluid-filled, simple ovarian cyst without septations or calcifications. The most common cause of a simple cystic mass in the reproductive age years is a physiologic cyst (luteal or follicular cyst). During the reproductive years the ovaries are functionally active, producing a dominant follicle in the first half of the cycle and a corpus luteum after ovulation in the second half of the menstrual cycle. Either of these structures, the follicle or the corpus luteum, can become fluid-filled and enlarged, producing a functional cyst. The most common complex adnexal mass in young women is a dermoid cyst or benign cystic teratoma. Most functional cysts can be managed expectantly, but surgery is indicated if certain characteristics are present. If the sonogram shows a simple cyst it is probably benign but careful follow-up is needed. During this period of observation the patient should be alerted to the possibility of acute onset of pain, which may be indicative of torsion of the adnexal cyst. Oral contraceptive medication can be used to help prevent further functional cysts from forming. Functional cysts should not form if the patient has been on oral contraception for at least 2 months because gonadotropins should have been suppressed. Polycystic Ovarian Syndrome the ovaries are bilaterally enlarged with multiple peripheral cysts (20-100 in each ovary). This is due to high circulating androgens and high circulating insulin levels causing arrest of folliclular development in various stages. This along with stromal hyperplasia and a thickened ovarian capsule results in enlarged ovaries bilaterally. Ovarian hyperthecosis refers to the presence of nests of luteinized theca cells in the ovarian stroma that may be steroidogenically active. As a result, the risks of endometrial hyperplasia and endometrial carcinoma are increased, especially in postmenopausal women. However, women with ovarian hyperthecosis have more severe hirsutism, with shaving being common. Virilization is frequent, with clitoral enlargement, temporal balding, deepening of the voice, and a male habitus. Most patients will have severe insulin resistance with high risk of type 2 diabetes mellitus and cardiovascular disease. Severe hirsutism and virilization in postmenopausal women are more often due to ovarian hyperthecosis than to virilizing ovarian tumors. Luteoma of Pregnancy Luteoma of pregnancy is a rare, non-neoplastic tumor-like mass of the ovary that emerges during pregnancy and regresses spontaneously after delivery. It is usually asymptomatic and is found incidentally during a cesarean section or postpartum tubal ligation. It can be hormonally active and produce androgens resulting in maternal and fetal hirsutism and virilization. They are associated with twins and molar pregnancies but they are only rarely associated with a normal singleton pregnancy. The natural course of these tumors is postpartum spontaneous regression and require only conservative managment. Pelvic examination is consistent with a 7-cm right adnexal mass, and there is lower abdominal tenderness but no rebound present. During the prepubertal and the postmenopausal years, functional ovarian cysts are not possible because ovarian follicles are not functioning. If sonography shows a complex adnexal mass in a girl or teenager, the possibility of germ cell tumors of the ovary has to be considered. Sudden onset of acute abdominal pain is a typical presentation of germ cell tumors of the ovary. These tumors characteristically grow rapidly and give early symptomatology as opposed to the epithelial cancers of the ovary that are diagnosed in advanced stages. Germ cell tumors of the ovary are most common in young women and present in early stage disease. In a prepubertal patient who is symptomatic and has ultrasound evidence of an adnexal mass, a surgical evaluation is recommended. If the ultrasound shows the consistency of the mass to be simple (no septations or solid components), this mass can be evaluated through a laparoscopic approach. If the mass has septations or solid components, a laparoscopy or laparotomy should be performed, depending on the experience of the surgeon. A unilateral salpingo-oophorectomy and surgical staging (peritoneal and diaphragmatic biopsies, peritoneal cytology, pelvic and para-aortic lymphadenectomy, and omentectomy) should be done. Follow-up after conservative surgery is every 3 months with pelvic examination and tumor marker measurements. Before the chemotherapy age the majority of these patients succumbed to their disease. An endovaginal sonogram in the emergency department confirms a 7-cm, mobile, irregular complex mass with prominent calcifications. The most common complex adnexal mass in young women is a dermoid cyst or benign cystic teratoma (discussed below). Patients in the reproductive age group with a complex adnexal mass should be treated surgically. The surgery can be done by a laparoscopy or a laparotomy according to the experience of the surgeon. At the time of surgery an ovarian cystectomy should be attempted to preserve ovarian function in the reproductive age. Patients were randomized (1:1:1) to one of two sotrastaurin groups or the control group. In nonconverted patients the tacrolimus target level from month 4 onward was 5 to 10 ng/mL. Voclosporin is structurally similar to cyclosporine with the exception of a modification at the amino acid­1 functional group. This modification results in a small molecule that is significantly more potent than cyclosporine in a calcineurin inhibition assay using human whole blood and in vivo in a rat heterotopic heart-transplantation model. Three trough concentration-adjusted exposure ranges of voclosporin were studied (low, mid, and high). Adult patients receiving a first deceased or living donor renal transplant were eligible for enrollment.

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