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The solid lines marked with Key Question numbers represent the questions that this review will evaluate in a comparative way (intervention vs blood pressure screening 12.5mg microzide with amex. The dotted line represents the evidence of a relationship between intermediate and health outcomes (which is beyond the scope of this review) arrhythmia ekg order generic microzide online. The bottom box represents Key Question 3 prehypertension in late pregnancy purchase microzide 25mg amex, which examines evidence on variation in outcome based on specific patient characteristics arteria spinalis anterior cheap microzide 25 mg on line. Analytic framework for catheter ablation for atrial fibrillation * Patients with longstanding persistent atrial fibrillation prehypertension food trusted microzide 25 mg, persistent atrial fibrillation pulse pressure and kidney disease purchase microzide 25mg with mastercard, or paroxysmal atrial fibrillation (considered separately); includes general population and Medicare population. The Key Informant panel included experts in cardiology primarily (with specialties in electrophysiology, heart failure, and cardiovascular aging/cardiovascular disease in older adults) and internal medicine; representatives from relevant specialty societies; government representatives. Reference lists of included articles and relevant review articles were inspected for relevant publications. For all Key Questions, the focus was on evidence from comparative studies with the least potential for bias. Comparisons of different techniques and/or approaches and mapping were beyond the scope of this report and thus were excluded. For Key Question 2, case series that were specifically designed to evaluate harms and/or adverse events following ablation, had a minimum of 1000 patients and at least 80 percent followup were included because all included comparative studies were relatively small in size. For all Key Questions, both long-term (>12 months) and short-term (12 months) outcomes were identified in included studies. Additional outcomes are reported in the detailed evidence synthesis sections of the Key Questions with a focus on outcomes common across studies. Studies published only as conference abstracts, non-English-language articles, and studies of nonhuman subjects were excluded. Study Selection Abstracts for all citations from the literature searches were independently reviewed by two team members and results were recorded in EndNote. All citations found to be potentially appropriate for inclusion by either reviewer underwent full-text review. Each full-text article was 10 independently evaluated for final inclusion by two investigators. A record of studies excluded at the full-text level with reasons for exclusion is included in Appendix C. After data extraction, at least one other staff member and one investigator each verified the accuracy and completeness of abstraction for each study included. Outcome measures and adverse events were prespecified during the creation of the extraction form to maintain consistency in data reporting. Special care was taken in the abstraction of information regarding crossover, the blanking period, reablation, and risk of bias. Basic information regarding technique, approach, provider and setting was also abstracted when reported in included studies. Limited data were extracted from case series with a focus on safety outcomes of interest. An outline of the specific information included in the data extraction forms are available in Appendix D and detailed evidence tables are included in Appendix E. Two investigators independently assessed the quality of each study and any discrepancies were resolved through discussion and consensus. Good-quality studies include clear descriptions of the population, setting, interventions, and comparison groups; a valid method for allocation of patients to treatment; low dropout rates and clear reporting of dropouts; appropriate means for preventing bias; and appropriate measurement of outcomes. These studies may not meet all the criteria for a rating of good quality, but no flaw is likely to cause major bias. The study may be missing information, making it difficult to assess limitations and potential problems. The results of some fair-quality studies are likely to be valid, while others may be only possibly valid. Studies rated as being poor in quality a priori were not excluded, but considered to be less reliable than higher-quality studies when synthesizing the evidence, particularly if discrepancies between studies were present. Data Synthesis When adequate data were reported in studies, meta-analysis was conducted in order to provide more precise estimates for outcomes. To determine the appropriateness of conducting meta-analysis, clinical and methodological diversity and assessed statistical heterogeneity were considered. A random-effects model was used to combine risk ratios for binary outcomes, mean differences for continuous outcomes. Random effects across studies were assumed and heterogeneity 2 among the studies was tested based on the random effect variance. Sensitivity analyses were conducted to assess the robustness of results in regards to treatment type (first-line vs. For continuous outcomes, results using the mean differences between followup scores were reported 33 as they are slightly more conservative and as the results based on mean difference in change score were similar. The outcomes listed below were considered to be the most relevant and were the focus of reporting, data pooling, and determination of overall strength of evidence. Outcomes such as pulmonary vein stenosis, cardiac tamponade, and pericardial effusion were considered to be attributable to ablation. Outcomes were reported as defined and definitions have been clarified as needed throughout the report. Detailed descriptions of these outcomes are available in the study characteristics tables in Appendix E. Some outcomes, particularly adverse events such as cardiac tamponade and pericardial effusion, are attributed to ablation, thus denominators for these outcomes reflect only patients who received ablation (either as randomized or after crossover from medical therapy). A final strength of evidence grade was assigned by evaluating and weighing the combined results of the above domains; final grades are presented in the Discussion, and tables detailing how final grades were determined are available in Appendix G. To ensure consistency and validity of the evaluation, the strength of evidence ratings for all key outcomes were reviewed by the entire team of investigators, and discrepancies were resolved by consensus. The strength of the evidence was then downgraded based on the limitations described above. We believe that additional evidence is needed before concluding either that the findings are stable or that the estimate of effect is close to the true effect. No evidence is available or the body of evidence has unacceptable deficiencies, precluding reaching a conclusion. Peer Review and Public Commentary Experts in atrial fibrillation and catheter ablation as well as individuals representing other important stakeholder groups were invited to provide external peer review of this Technology Assessment. At the end of this period, the authors considered both the peer and public review comments and generated a final report. A total of 3,471 potentially relevant citations were identified, of which 3,310 came from database searches and 161 were added after reviewing the bibliographies of previous reports and relevant articles. After dual review of abstracts and titles, 3,368 articles were excluded (14 of which were identified from the updated literature search and were already included in the report). Also summarized under this comparison for Key Question 2 only were an additional 17 case-series, 55-71 included specifically for information regarding the safety of catheter ablation. A total of 53 articles that did not meet one or more of the inclusion criteria were excluded after full-text review. One, five, six, and four studies were excluded because they did not include populations, interventions, comparisons, and outcomes of interest, respectively. The remainder were excluded for the following reasons: cases series with less than 1000 patients (n=8); comparative observational study with less than 100 patients (7 studies); same population as prior included study (6 studies); did not address any of the Key Questions (1 study); and duplicate publication (1 study). Total Citations Total (n=3,471) Database searches (n=3,310) Previous reports (n=161) 2. Of the comparative observational studies, two included Medicare populations (patients 65 years of age). This, combined with possible clinical heterogeneity across studies, limits the ability to draw firm conclusions. Only one trial reported that this persisted to 12 months (low strength of evidence). This study had substantial crossover from medical therapy to cryoballoon ablation. Conflicts of interest were mainly in the form of grants or consulting fees from biomedical companies. Patients underwent treatment as a first-line 35, 40, 42, 46 therapy in three trials, as a second-line therapy. In many studies, the adequacy of anticoagulation in the ablation group, particularly before ablation, was not clear. Limited detail regarding anticoagulation in the medical treatment groups was available. Details regarding ablation and mapping techniques used in each trial are outlined in Table H6 in the Appendix. In some studies, a patient had to fail at least two drug treatments in order to be eligible for crossover. One trial did not provided the number of patients that crossed over, but indicated that followup could not be extended to 12 months in the medical therapy group because many went on to have 37 40 ablation. One study did not report if crossover occurred and two did not allow crossover 36, 46 during the 12-month study period. Common methodological shortcomings included unclear allocation concealment 45 (only one documented concealed allocation) and lack of assessor blinding for primary 38, 41, 44, 83 outcomes. Discrepancies in baseline characteristics as well as unclear randomization methods were observed, although rarely. Of these, three reported outcomes up to 12 months 49, 52, 54 following the blanking period and four reported on outcomes after 12 months (15 to 69 48, 50, 51, 53 49, 52, 54 months). Funding was not 48, 51, 53, 54 50 reported for four studies; one study was supported by Biosense Webster and two received government grants/funds (the Health Research Foundation/Health Bureau of 49 Chongquing and the National Science Foundation of China and Beijing Natural Science 52 Foundation). Ablation strategies varied (details regarding ablation and mapping techniques used in each study are outlined in Table H6 in the Appendix). The most common methodological shortcoming was a lack of assessor blinding for primary 48, 52, 54 outcomes. Followup of at least 80 percent was reported by three studies and all of them controlled for confounding (primarily in the form of similar baseline characteristics between 49-54 groups). Only the group that underwent pulmonary vein antrum isolation was included; the atrioventricular junction ablation group was excluded from our analysis per our prespecified exclusion criteria. The majority of patients across studies were male with mean ages ranging from 51 to 64 years old. Overall, all-cause mortality within 12 months was rare across the seven trials, ranging from 0 to 3. One trial reported no mortality in either treatment group, the other 35 reported two deaths (1. Of the six included observational studies, three reported all-cause mortality (Table 9). In one poor-quality study with a mean followup of 16 months, no patient died in the ablation arm and one patient (1. In the second study, conducted in a Medicare-relevant population (mean age 67 years), three patients (2. Two studies reported 35, 42 cardiovascular mortality up to 24 months past the 30 day periprocedural time. Study sizes were likely insufficient to effectively determine risk of cardiovascular mortality or detect statistical differences between treatment groups. Cardiovascular mortality was rare at both 12-month and 24-month time frames (Table 8). Both deaths were from myocardial infarction and not attributed to 34 38, 46, 47 treatment. This death occurred in the study that was 39 restricted to patients with heart failure. Two observational studies, both conducted in Medicare-relevant populations (age 65 years), assessed cardiovascular mortality greater than 30 days from treatment (Table 9).

Identication of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction blood pressure iphone buy microzide 25 mg with visa. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial utter blood pressure medication yeast infections cheap microzide 12.5mg online. A clinical study of the application of endocardial fulguration in the treatment of recurrent atrial utter blood pressure chart for excel purchase genuine microzide line. Identication of a critical zone in the reentrant circuit by endocardial mapping techniques blood pressure pulse 95 25mg microzide with amex. Radiofrequency ablation of the inferior vena cava-tricuspid valve isthmus in common atrial utter arteria radial order 25mg microzide amex. Hospital ization for arrhythmias in the United States: Importance of atrial brillation arrhythmia nausea order online microzide. Mapping and radiofre quency ablation of intraatrial reentrant tachycardia after the Senning or Mustard procedure for transposition ofthe great arteries. Fatkin D, MacRae C, Sasaki T, et al: Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. Prevalence, incidence, prognosis, and predisposing conditions for atrial brillation: population-based estimates. Atrial brillation as an independent risk factor for stroke: the Framingham Study. Electrocardiographic patterns and results of radiofrequency catheter ablation of clockwise type I atrial utter. Saoudi N, Cosio F, Waldo A, et al: A classication of atrial utter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from the Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Importance of atrial utter isthmus in postoperative intra-atrial reentrant tachycardia. Role of right atrial endocardial 160 Curr Probl Cardiol, March 2005 structures as barriers to conduction during human type I atrial utter. Nakagawa H, Lazzara R, Khastgir T, et al: Role of the tricuspid annulus and the eustachian valve/ridge on atrial utter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identication of ablation success. Activation and entrainment mapping denes the tricuspid annulus as the anterior barrier in typical atrial utter. The upper link of human common atrial utter circuit: denition by multiple endocardial recordings during entrain ment. Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycar dia. Reversal of reentry and acceleration due to double-wave reentry: two mechanisms for failure to terminate tachycardias by rapid pacing. Brugada J, Boersma L, Kirchhof C, et al: Double-wave reeentry as a mechanism of acceleration of ventricular tachycardia. Brugada J, Brugada P, Boersma L, et al: On the mechanisms of ventricular tachycardia acceleration during programmed electrical stimulation. Acceleration of typical atrial utter due to double-wave reentry induced by programmed electrical stimulation. Right atrial utter due to lower loop reentry: mechanisms and anatomic substrates. Zhang S, Younis G, Hariharan R, et al: Lower loop reentry as a mechanism of clockwise right atrial utter. Electrocar diographic and electrophysiologic characterization of atypical atrial utter in man: Curr Probl Cardiol, March 2005 161 use of activation and entrainment mapping and implications for catheter ablation. Activation patterns in experimental canine atrial utter produced by right atrial crush injury. Ouyang F, Ernst S, Vogtmann T, et al: Characterization of reentrant circuits in left atrial macroreentrant tachycardia: critical isthmus block can prevent atrial tachy cardia recurrence. Bochoeyer A, Yang Y, Cheng J, et al: Surface electrocardiographic characteristics of right and left atrial utter. Atrial macroreentry involving the myocardium of the coronary sinus: a unique mechanism for atypical utter. Rapid atrial stimulation: successful method of conversion of atrial utter and atrial tachycardia. Comparative efficacy of intravenous ibutilide versus procainamide for enhancing termination of atrial utter by atrial overdrive pacing. Efficacy of intravenous propafenone in termination of atrial utter by overdrive transesoph ageal pacing previously ineffective. Doni F, Della Bella P, Kheir A, et al: Atrial utter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone. Comparison of atrial overdrive pacing with and without extrastimuli for termination of atrial utter. Giorgberidze I, Saksena S, Mongeon L, et al: Effects of high-frequency atrial pacing in atypical atrial utter and atrial brillation. Doni F, Manfredi M, Piemonti C, et al: New onset atrial utter termination by overdrive transoesophageal pacing: effects of different protocols of stimulation. Restoring sinus rhythm in patients with atrial utter and brillation: pharmacologic or electrical cardioversion Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial utter and atrial brillation. Emergency management of atrial brilla tion and utter: intravenous diltiazem versus intravenous digoxin. A placebo controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial brillation and atrial utter: a multicenter study. Intravenous diltiazem for the treatment of patients with atrial brillation or utter and moderate to severe congestive heart failure. Comparison of intravenous diltiazem and verapamil for the acute treatment of atrial brillation and atrial utter. Esmolol versus verapamil in the acute treatment of atrial brillation or atrial utter. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial brillation or utter: a double-blind randomized cross-over study. Delle Karth G, Geppert A, NeunteuT, et al: Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Electrophysiologic substrates and modes of initiation and termination Am J Cardiol 1980;45:732-41. Prospective comparison of ecainide versus quinidine for the treatment of paroxysmal atrial brillation/utter. Short and long-term efficacy and safety of ecainide acetate for supraventricular arrhythmias. Efficacy of dofetilide in the treatment of atrial brillation-utter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy. Kottkamp H, Hugl B, Krauss B, et al: Electromagnetic versus uoroscopic mapping of the inferior isthmus for ablation of typical atrial utter: a prospective randomized study. Optimizing the detection of bidirectional block across the utter isthmus for patients with typical isthmus-dependent atrial utter. Reithmann C, Hoffmann E, Spitzlberger G, et al: Catheter ablation of atrial utter due to amiodarone therapy for paroxysmal atrial brillation. Catheter ablation of typical atrial utter: a randomized comparison of 2 methods for determining complete bidirec tional isthmus block. Differential pacing for distinguishing block from persistent conduction through an ablation line. Isoproterenol to evaluate resumption of conduction after right atrial isthmus ablation in type I atrial utter. Electrophysiological effects of catheter ablation of inferior vena cava-tricuspid annulus isthmus in common atrial utter. Radiofrequency ablation of intra-atrial reentrant tachycardia after surgical palliation of congenital heart disease. Left atrial utter after segmental ostial radiofre quency catheter ablation for pulmonary vein isolation. Left atrial utter after radiofrequency catheter ablation of focal atrial brillation. Acute coronary occlusion during radiofrequency catheter ablation of typical atrial utter. Acute pulmonary edema after successful electrical cardioversion of atrial brillation. Kirkorian G, Moncada E, Chevalier P, et al: Radiofrequency ablation of atrial utter. Randomized study comparing radiofrequency ablation with cryoablation for the treatment of atrial utter with emphasis on pain perception. The risk of atrial brillation following radiofrequency catheter ablation of atrial utter. Da Costa A, Romeyer C, Mourot S, et al: Factors associated with early atrial brillation after ablation of common atrial utter. Electrical remodeling of the atria associated with paroxysmal and chronic atrial utter. Electrical remodeling of the atrium in an anatomic model of atrial utter: relationship between substrate and triggers for conversion to atrial brillation. Omran H, Jung W, Rabahieh R, et al: Left atrial appendage function in patients with atrial utter. Sakurai K, Hirai T, Nakagawa K, et al: Left atrial appendage function and abnormal hypercoagulability in patients with atrial utter. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology. Frequency-dependent breakdown of wave propagation into brillatory conduction across the pectinate muscle network in the isolated sheep right atrium. Mechanisms of atrial utter and atrial brillation: distinct entities or two sides of a coin First published 1997 Second edition 2002 Third edition 2006 Library of Congress Cataloging-in-Publication Data Taylor, George Jesse. The medica tions described do not necessarily have specific approval by the Food and Drug Administration for use in the diseases and dosages for which they are recommended. Because standards for usage change, it is advisable to keep abreast of revised recom mendations, particularly those concerning new drugs. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. Training programs are placing an ever-increasing clinical load on their faculties. My brief discussion emphasizes daily issues in clinical medicine, as well as material that you may encounter on Board exams (Internal Medicine, Family Practice, Flex, and National Boards). I again acknowledge that Marilyn Taylor is a patient woman, and I appreciate her forbearance during this writing adventure. It is the approach cardiologists have taught generations of students, and it works. As you gain experience, you will develop this ability, and you will be tempted to focus immediately on the gross abnormalities that seem to jump out of the page. Regardless of your ability and experience, if you do not focus on the rate, rhythm, intervals, and axis, you will miss subtle and important abnormalities. Not addressing intervals, for example, would be like omitting the family history from a history and physical exam. The beauty of the history and physical examination format is that it allows you to collect meaningful data, even when the patient has an illness that you do not understand. I will avoid lengthy description of technical areas such as the origin of lead systems. My goal is to provide brief yet clear explanations, and to get you through the introductory material as quickly as possible. The gain can be changed so that high-voltage complexes fit on the paper, or so that low-voltage complexes are magnified. Changing the gain is uncommon, but it would be apparent from the calibration marker. Having 12 leads grouped in frontal and horizontal planes allows us to reconstruct electrical events in three dimensions1. The vectorcardiogram, popular 40 years ago and seldom used now, displayed the wave of depolarization in three dimensions, using x, y, and z axes. For example, if depolarization pro gresses from the right side of the heart to the left, the net voltage is positive in lead I1. The general direction of the wave of depolarization, the orientation of its vector in space, is referred to as the electrical axis. Leads that have an inferior orientation are best at detecting changes from the inferior surface of the heart. Anterior precordial leads are most sensitive in detecting anterior wall changes, and the lateral leads, lateral wall abnormalities.

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Alternatively heart attack or stroke 12.5mg microzide fast delivery, epinephrine can be given into a catheter placed in the umbilical vein low blood pressure chart nhs cheap microzide 12.5 mg line. This route will likely deliver more effective blood levels of the drug pulse pressure low values buy cheap microzide 12.5mg on line, but additional time is required to insert the catheter heart attack cpr purchase 25mg microzide overnight delivery. Thirty seconds following administration hypertension classification jnc 7 buy microzide uk, an increase in heart rate to more than 60 bpm should be observed pulse pressure 55 mmhg purchase 12.5mg microzide with visa. If the heart rate remains depressed (<60 bpm) repeat doses of epinephrine may be given every 3 to 5 minutes. In the meantime, good chest movement, equal bilateral breath sounds, and well coordinated chest compressions to an appropriate depth must all be ensured. If the infant displays pallor, poor perfusion and/or there is evidence of blood loss, hypovolemic shock should be considered in the infant who has not responded to resuscitative efforts. The recommended solution for acutely treating hypovolemia in the newly born infant is normal saline. Volume expanders must be given intravenously, usually through an umbilical vein catheter, although the intraosseous route can also be used. If the heart rate is detectable but remains below 60 bpm after administering adequate ventilation, chest compressions, epinephrine, and volume expanders, the possibility of metabolic acidosis should be considered. Moreover, mechanical causes of poor response including airway malformation, pneumothorax, and diaphragmatic hernia or congenital heart disease should also be considered. If the heart rate remains absent after 15 minutes of resuscitative efforts (establishing an airway, delivering positive pressure ventilation, administering chest compressions, administering epinephrine, addressing the possibilities of hypovolemia, acidosis, congenital airway malformation or congenital heart disease) discontinuation of resuscitation may be appropriate (2). A one minute Apgar score of 8 is usually due to a zero score for color since truncal cyanosis is still present at one minute. A 5 minute Apgar score of 9 is normal because acrocyanosis of the feet persists for some time past five minutes. Low Apgar scores at five and ten minutes may reflect birth depression and/or need for resuscitation. Page 83 Apgar Scoring Score 0 1 2 Heart rate Absent <100 >100 Respiratory effort Absent Slow, irregular Good, crying Muscle tone Limp Some flexion Active motion Reflex irritability No response Grimace Cough or sneeze Color Blue Extremities blue Completely pink Questions 1. Name three major physiologic changes that must occur in the newborn shortly after birth in order to transition to extrauterine life. What three elements of the newborn physical examination are reassessed every 30 seconds during resuscitation until the infant is stable Ideally, how many caregivers should be available for the resuscitation presented in the case vignette What is the most important step in cardiopulmonary resuscitation of the compromised newborn infant International Guidelines for Neonatal Resuscitation: An Excerpt From the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Intrapartum risk factors: emergency cesarean section, non-reassuring fetal heart tones, use of general anesthesia, narcotics administered to mother within 4 hours of delivery, and abruptio placentae. Fluid in alveoli is absorbed and air fills the air sacs, umbilical cord is clamped disconnecting the infant from the placental circulation and pulmonary vasculature must relax allowing increased pulmonary blood flow and decreased right-to-left shunting. Ventilation of the lungs is the most important and most effective step in cardiopulmonary resuscitation of the compromised newborn infant. If the infant continues to be apneic, is gasping, has a heart rate of less than 100 bpm and/or has persistent central cyanosis despite 100% free flow oxygen, then positive pressure ventilation with a bag and mask should be administered. Noticeable chest wall rise, bilateral breath sounds and improved color and heart rate are indications that ventilation is adequate. Three compressions should be administered for every one assisted ventilation so that 90 compressions plus 30 breaths are given each minute. It can be administered through an endotracheal tube or through an umbilical vein catheter. Maternal history is remarkable for a single prenatal visit in the first trimester. A decision is made to deliver the infant by cesarean section following maternal treatment with betamethasone. The risk factors identified in the above scenario include poor prenatal care, severe preeclampsia, prematurity, oligohydramnios, and intrauterine growth restriction. For the pediatrician, detailed knowledge of the maternal and pregnancy history is critical to providing timely and comprehensive care to the infant. A high risk pregnancy can be defined as any pregnancy where maternal and/or fetal conditions may lead to an adverse perinatal outcome. A pregnancy may be identified as high risk during the antepartum or intrapartum period. Indeed, lack of, limited, or late prenatal care, in and of itself, is a common high risk condition seen in urban perinatal centers. Screening tests for certain high risk problems such as diabetes, genetic conditions, and congenital anomalies are either routinely or selectively performed during the antepartum period for early recognition and intervention. This chapter will focus on a few of the more common pregnancy complications with an emphasis on neonatal outcome. The World Health Organization defines preterm delivery as a delivery that occurs between 20 and 37 weeks gestational age. After reviewing the list above, it is readily apparent that preterm delivery is the common denominator for many high risk conditions of pregnancy. Timely detection of preterm labor and delivery allows for prompt referral of the mother to a facility where more intensive surveillance, monitoring, and care for both mother and newborn can be accomplished (2). Studies assessing prevention methods such as education and surveillance programs and home uterine activity monitoring have demonstrated no benefit in reducing the frequency of preterm birth. Other strategies involved in the treatment of preterm labor are: cervical cerclage, tocolytics (beta sympathomimetics such as terbutaline and ritodrine, magnesium sulfate, prostaglandin synthetase inhibitors such as indomethacin), and antibiotics. Of these, the most frequently used methods at Kapiolani Medical Center for Women and Children are cerclage, terbutaline, magnesium sulfate, and antibiotics. Although it has been difficult to demonstrate the efficacy of tocolytics and antibiotics in clinical trials for preterm labor, these agents may provide a 48 hour latency period during which antenatal corticosteroids can be administered. It involves placing a suture circumferentially around the internal cervical os between 12-14 weeks gestation. Maternal risks associated with cerclage placement include the risk of anesthesia, bleeding, infection, rupture of membranes, maternal soft tissue injury, and spontaneous suture displacement. Terbutaline, the most commonly used beta sympathomimetic, stimulates the beta-2 receptors found in the uterus. Potential fetal side effects of beta-2 agonists include elevation in baseline heart rate, rhythm disturbances, septal hypertrophy, and hypoglycemia. Magnesium sulfate affects uterine activity by decreasing the release of acetylcholine and altering the amount of calcium pumped out of myometrial cells. Respiratory and motor depression can occur in the neonate with high maternal magnesium levels. In general, side effects to the fetus and neonate are minimal when compared to beta sympathomimetics. Given the role of prostaglandins in labor, indomethacin would seem a logical choice for a tocolytic agent. Reported fetal side effects include oligohydramnios secondary to decreased fetal urine output, ductal constriction with the potential for subsequent persistent pulmonary hypertension in the neonate, and necrotizing enterocolitis. The use of indomethacin is restricted to pregnancies at <30-32 weeks gestation and for a treatment period of less than 48 hours. Ampicillin and erythromycin have been shown to increase the latency period from the time of rupture of membranes to delivery with significant neonatal benefits (1). The incidence of neonatal mortality and morbidity increases with decreasing gestational age. Although it is outside the scope of this chapter to address the multiple medical, psychosocial, neurodevelopmental and financial problems associated with prematurity, it should be emphasized that the "borderline viable" population of infants (<25 weeks gestational age) remain the greatest challenge. Due to their statistically poor outcomes, the question of whether or not to provide life supportive measures in the delivery room is, ideally, discussed with the prospective parents prior to delivery. The management of these most fragile newborns remains an ongoing area of controversy and debate in neonatal medicine. Preeclampsia is defined as new onset gestational hypertension with proteinuria, with or without edema. It complicates approximately 8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality. Uteroplacental ischemia mediated by the renin-angiotensin system is one of the most fundamental abnormalities of this disorder, however, the etiology of Page 85 preeclampsia is still unknown. Predisposing factors include primiparity, younger and older age extremes, familial/genetic factors, twin gestation, diabetes, and non-immune hydrops fetalis. Additional and alternative treatment strategies such as antihypertensives and magnesium sulfate for prevention of seizures are commonly employed especially when the degree of fetal immaturity (balanced with maternal status) precludes immediate delivery. The increase in perinatal morbidity and mortality associated with preeclampsia is largely due to prematurity. Uteroplacental insufficiency and abruptio placenta contribute to poor outcomes (3). Fetal intrauterine growth restriction is a frequent and expected by product of uteroplacental ischemia. Interestingly, despite the increase in fetal growth restriction and prematurity, preeclampsia is associated with a decreased risk of cerebral palsy (4). Diabetes mellitus is classified as type 1 (lack of insulin production or pre-gestational), type 2 (adult onset, insulin resistance). An elaborate and more detailed classification system for diabetes in pregnancy was developed by Priscilla White and later modified where type A1 is described as gestational diabetes treated with diet, and type A2 requires insulin therapy. Gestational diabetes is defined as carbohydrate intolerance first recognized during pregnancy. It accounts for the majority (80-90%) of the 3-5% of pregnancies complicated by diabetes and is caused by a 60% decrease in peripheral insulin sensitivity (a normal phenomenon in pregnancy), for which some women cannot compensate. Because this condition is often asymptomatic, screening is indicated between 24 and 28 weeks gestation. Glucose management is strict with the recommendation to maintain levels between 60 and 120 mg/dl. It is well established that tight metabolic control is associated with a marked reduction in the fetal and neonatal complications associated with diabetes in pregnancy listed in the table below: Fetal and Neonatal Complications of Diabetes in Pregnancy: A. Macrosomia occurs in 25%-45% of pregnancies complicated by diabetes which is a direct result of fetal hyperglycemia and hyperinsulinemia. Neonatal management of all infants of diabetic mothers includes a thorough evaluation for birth trauma and congenital defects, screening for and management of hypoglycemia, and close scrutiny of the infant for signs of respiratory distress. This condition presents the greatest clinical challenge to the pediatrician because prevention and treatment strategies are either nonexistent or unsatisfactory. Agent specific neonatal outcomes are frequently confounded by polysubstance abuse, poor nutrition, poor health care and unsatisfactory home environments. In Hawaii, the most commonly abused drugs are alcohol, marijuana, amphetamines, and methamphetamines. Additional substances of abuse include cocaine, heroin, and miscellaneous other agents. As a general rule, the severity and frequency of fetal/neonatal side effects associated with maternal substance abuse is related to timing, dose, and duration of use. Heroin has been one of the best studied and well characterized due to its prolonged existence as an illicit drug. Complications of heroin addiction in pregnancy include an increased incidence of stillbirth, preterm birth, and the delivery of infants who are small for gestational age. Neonatal abstinence syndrome (symptoms of withdrawal) occur in 50%-75% of infants and usually begin within 48 hours after birth and consists of a combination of irritability, jitteriness, coarse tremors, high pitched cry, sneezing, yawning, tachypnea, poor feeding, vomiting, diarrhea, sweating, temperature instability, hyperreflexia, and, occasionally, seizures. A scoring system has been devised using the above symptoms to assist with the management of these infants. Pharmacotherapy for severe withdrawal symptoms include tincture of opium, phenobarbital, and methadone. The use of naloxone is strictly contraindicated as it can lead to acute, severe withdrawal and seizures. Methadone withdrawal seen in infants of mothers under treatment for heroin addiction has many similar characteristics to heroin abstinence syndrome. Methadone is associated with both delayed onset and increased severity of withdrawal symptoms, including seizures. Exposure during pregnancy may result in a spectrum of symptoms secondary to varying degrees of insult to the central nervous system. Microcephaly, mild to moderate mental retardation, subtle cognitive and behavioral deficits have all been well described. No consistent or specific complications have been associated with the use of marijuana in pregnancy. Adverse pregnancy outcomes associated with cocaine abuse include higher incidence of stillbirth, asphyxia, prematurity, and babies with low birth weight and smaller heads. Breastfeeding is contraindicated as cocaine intoxication has been demonstrated in breast fed infants. Abuse of either amphetamine or methamphetamine during pregnancy is associated with a higher incidence of perinatal mortality, prematurity, and growth deficits. Abnormal central nervous system findings including cystic encephalomalacia and hemorrhage have also been described (6). Selective drug screening of mothers and newborns takes place routinely at most perinatal centers. Decisions regarding who to screen is often related to other perinatal risk factors such as inadequate prenatal care, previous history of substance abuse, high risk clinical signs in the mother (inappropriate or unusual behavior), history of prostitution, history of preterm labor, and presence of sexually transmitted disease(s).

Although the precise active in response to low oxygen stress (Guillemin and Krasnow pulse pressure 79 purchase microzide on line, cellular and molecular site of phthalate action in the fetal male is 1997; Semenza arteria rectal superior purchase generic microzide pills, 1994; Wenger and Gassmann blood pressure 3rd trimester generic microzide 12.5mg line, 1997) arteria gastrica sinistra cheap microzide express. It appears that the mechanism of action of 1991; Isaac and Andrew arteria genus purchase genuine microzide on-line, 1996) pulse pressure 60 mmhg order microzide with a visa, regulation of circadian clocks phthalate-induced toxicity is widespread throughout vertebrates. Some of these responses do not easily t the traditional although it failed to induce estrogenlike responses in this species. Instead, the criteria listed at the end of this chapter different brain regions were measured. Because such information is less available system, its role, if any, in normal development is unknown, and for studies in wildlife, more leeway was used in determining there is as yet no direct evidence for an implication of the AhR in whether to include ndings in wildlife than in humans. Treated progeny populations of several sensitive bird species declined because of displayed transient reductions in ventral prostate and seminal vesicle unsuccessful incubation of eggs due to abnormally thin egg shells weights, and epididymal sperm reserves and glans penis size were (Cooke, 1973). Ejaculated sperm numbers were reduced (45% cormorant) have experienced dramatic population increases since in the 0. Suggested mated successfully with a control male; 20% of the F1 treated females mechanisms have included 1) limiting the supply of calcium to the did not become not pregnant (Wolf et al. In the F2, survival through for shell formation via inhibition of carbonic anhydrase (Bitman et weaning was drastically reduced (15% treated vs. At the age when sexual behavior was tested, AhR potency of these congeners in causing egg shell thinning. In both strains, atrazine disrupted the regular 4-day estrous transport of calcium from the eggshell gland mucosa to the lumen cycles. Many of these biochemical end points are associated with elevated serum progesterone and low E2 interrelated, and it is difficult to determine which are the direct concentrations, indicative of a repetitive pseudopregnant condition. The delayed ovulation, in turn, allows prolonged Concern for the endocrine-disrupting effects of atrazine, a triazine exposure to estrogens and an effect evident as persistent vaginal herbicide, arose following the observation of increased incidence of cornication. Rather, appeared in control females but occurred earlier in the treated reproductive aging in the Fischer 344 is believed due to inability to females. Daily exposure of adult Fischer beginning on postnatal day 23 delayed preputial separation. At rats to 120 mg/kg for 7 days resulted in fewer treated females postnatal day 53, ventral prostate weights, but not testes weights, displaying normal estrous cycles, and the number of days in were reduced in rats treated with 50 mg/kg/day. Fertility was reduced in somewhat less sensitive, as it required 50 mg/kg/day to delay vaginal females during the first week after exposure, but pregnancy opening, and 100 mg/kg/day altered estrous cycles in the rst 15 outcome was not affected in those that became inseminated (Simic days after vaginal opening. In addition, progesterone receptor binding and uterine peroxidase (Connor et similar exposures reduced their ability to respond to the priming al. In this same study, atrazine did not affect basal or E2 effect of ovulated female salmon urine. However, even with the close neurotransmitter function has also been reported in croaker after interactions between the nervous and endocrine systems, it has exposure to lead (Thomas and Khan, 1997). Although the mechanisms by the present context for both toxicological and neurobiological reasons. Some hormones with neural function must be considered: 1) effects hormones, such as sex steroids or thyroid hormones, are known to related to activational properties of hormones in adult organisms have a strong and strictly time-coupled organizational impact on brain resulting in transient changes and 2) organizational effects on development (Gray and Ostby, 1998). From a neurobiological point hormone-dependent processes during neural development that can of view, disruption of organizational factors during development in result in permanent changes of neurobehavioral function, general and, more specically, during brain development is important particularly sex-dependent and sexual-related behaviors. Both because long-lasting or irreversible neurobehavioral changes later in actions may involve specic hormone receptors, such as the estrogen life may be the consequence of such interactions (Tilson, 1998). In humans, endemic cretinism caused by iodine coupled to second messengers (Mensah-Nyagan et al. However, the degree example, prenatal/neonatal exposure to the 3,4,3,4tetrachloro of thyroid dysfunction is clearly critical. In both cases, the changes persisted into neurobehavior, or if sexually dimorphic nonreproductive behavioral adulthood (Seegal et al. The study suggested that the changes following chemical exposure are reported without endocrine reductions in brain dopamine concentrations were a consequence of data. Alterations of hormone concert with changes in cholinergic receptor function, whereas the concentrations may be caused by cytotoxic effects on hormone persistent elevations in brain dopamine may be mediated by producing organs, resulting in impaired synthesis or release of alterations in steroid hormone function during key developmental hormones. Coplanar congeners, in addition to their ability to interact at lesions in the thyroid and inhibition of proteolysis of thyroglobulin, the AhR, also alter estrogenic function, either by enhancing the thereby decreasing the release of T4 (Collins and Capen, 1980). In metabolism of estrogens to hydroxy and catecholestrogens (Gierthy addition, thyroid hormone levels are influenced by increase in et al. Glucocorticoids also inhibit the detected in all mammal brains so far examined (Lephart, 1996), production of many cytokines. In addition, glucocorticoids inhibit but its role in sexual differentiation in other than rodent species the expression of adhesion and adhesion receptor molecules on the remains to be proven. Hypoprolactinemia is associated with impaired lymphocyte maximum activity (Lephart, 1996; Lauber et al. The endogenous opioid peptides region with several sexually dimorphic nuclei (Cooke et al. Endorphin receptors similar to those in the brain that declines to basal activity within the first 5 days after birth are present on spleen cells and probably several others types of (Lephart, 1996). One biological activity of the according to the congener pattern found in breast milk and thymus that is under neuroendocrine control is the secretion of containing ortho-chlorinated and coplanar congeners, caused thymic hormones (Savino and Arzt, 1999). The interaction between the pituitary testosterone levels in adult male offspring (Hany et al. Sweet and thymus is demonstrated by the immunodeficiency of the preference behavior is more pronounced in female rats, suggesting thymus-dependent immunity that occurs in mice following that reductions in hypothalamic E2 results in a more femalelike injection with antisomatotrope hormone serum. The balance between male and female sex hormones, E2 and testosterone, influences the extent of 3. In general, the male sex hormone the major function of the immune system is to defend against testosterone is immunostimulatory. The maintenance of homeostasis requires atrophy, suppression of thymus-dependent cellular immune bidirectional communication between the neuroendocrine and responses, acceleration of autoimmune diseases, suppression of immune systems. Most of the influence of the brain on the natural killer cell activity, myelotoxicity, and stimulation of the immune system is exerted by hormones released by the mononuclear phagocyte system (Luster et al. Indeed, receptors for hormones have been changes are seen in lymphoid organs during pregnancy, and detected on cells of the immune system, whereas receptors for increased serum E2 levels during pregnancy correlate with cytokines have been detected in the endocrine glands and brain. It lymphopenia and suppression of cellular immunity (Clarke, is also noteworthy that almost all lymphoid tissues are innervated, 1984). By evaluation of steroidal and nonsteroidal compounds although the role of this neuroregulatory pathway is largely with varying degrees of estrogenicity, Luster et al. Other capacity to generate a cortisol response is decreased, suggesting that mechanisms are those mediated by the direct action of this represents an adaptational response of the immune system that neuropeptides, such as opioid peptides (Van den Berg et al. For their immune system during this delicate developmental period communication, cells of the immune system carry receptors for a (Kavelaars et al. Histologically, the thymus is developing and mature immune system and that these may be the first organ affected by this hormone. It is characterized by blackheads or whiteheads, pimples, oily skin, and possible scarring. Patients rarely, if ever, complain about reduced sebum production, but elevated sebum production, yielding oily skin that can be a precursor to acne, is a common complaint. It is a very common skin disorder which can present with inflammatory and non inflammatory lesions chiefly on the face but can also occur on the upper arms, trunk, and back. Age, in particular, has a significant and well-known impact, as sebum levels are usually low in childhood, rise in the middle-to-late teen years, and remain stable into the seventh and eighth decades until endogenous androgen synthesis dwindles. Sebum, the oily secretion of the sebaceous glands containing wax esters, sterol esters, cholesterol, di and triglycerides, and squalene, imparts an oily quality to the skin and is well known to play an important role in acne development. The pimples and bumps heal slowly, and when one begins to go away, others seem to crop up. Acne may cause scarring of the skin, but generally causes no long-term health problems. Existence of even a minor lesion in this part may be unpleasant for the patient and seems large. This image can cause mental disorders including depression and anxiety, low self-esteem, and decrease in social relationships. However, high levels of anxiety and depression in patients with facial acne are not related to oxidative stress, according to a study published online in the Journal of Cosmetic Dermatology. The roots of acne have been traced all the way pimples would then fall from the body. Acne at that time swellingand is described to be treated with some animal was also contributed to witchcraft. Ancient Egyptians around 3rd these pimples, different type of mercury makeup was also in century was of the opinion that acne is caused by telling lies. Hence forth, people Tutankhamun, Egyptian Pharaoh of the 18th dynasty had acne restored to the sulfur treatments of antique times. Retin-A has produced great results and is still in Polycystic Ovary Syndrome (Pcos); use. Microneedling with Methicillin-Resistant Staphylococcus Aureus (Mrsa); dermaroller emerged as a novel treatment modality for the treatment of acne scars. Blackheads -open plugged pores and although it usually manifests during puberty and worsens 3. Papules-Small red, tender bumps throughout adolescence, epidemiological studies suggest that 4. Pimples-pustules, which are papules with pus at their tips it can arise at any age. Nodules-Large, solid, painful lumps beneath the surface of the results from sebaceous gland hyperplasia, abnormal follicular skin differentiation with increased keratinization, microbial hyper colonization of the follicular canal, and increased inflammation 6. Cystic lesions-Painful, pus-filled lumps beneath the surface of primarily through activation of the adaptive immune system the skin may also be contributors. Acne treatment aims to lessen the inflammatory or non-inflammatory Acne Vulgaris (Av); acne lesions, improve appearance, prevent or minimize potential Aquaporin-3 (Aqp3); adverse effects, and minimize any scarring. Pharmacological Dehydroepiandrosterone (Dhea); therapy is not always desirable because of the development of antibiotic resistance or the potential risk of adverse effects. Complementary and Alternative Medicine (Cam); Non-pharmacological therapies can be viable alternatives for Insulin-Like Growth Factor 1 (Igf-1); conventional therapies. It is widely agreed, however, that the mild and (d) An inflammatory response caused by the immunological moderate forms of acne display primary lesions only, while severe activity of P. It the adequate control of the four pathogenic mechanisms is noteworthy that acne severity and scarring have been related to involved in the appearance of acne lesions is key to treatment P. Several exacerbating factors have been suggested as allergens, toxins, or porphyrins, and enzymes. Acne is always including diet, menstruation, sweating, personal stress, accompanied by a variety of other signs and symptoms such as ultraviolet radiation, application of pomades and occupation [8]. Use of medications like lithium, steroids, and anticonvulsants, Furthermore, acne causes significant psychological morbidity in exposure to excess sunlight, use of occlusive wear like shoulder affected patients. Currently available systemic products include pads, headbands backpacks, and underwire brassieres, endocrine the retinoid isotretinoin, antibiotics, or oral contraceptives, disorders like polycystic ovarian syndrome and even pregnancy all of which are indicated for more severe acne, acne resistant have also reported [26]. The association between diet and acne to other therapies, and nodulocystic, scarring acne. Commonly used high glycemic index is rapidly absorbed, increases serum glucose treatments aim to reduce the number of inflammatory lesions, levels and stimulates increased glucose-dependent insulin inhibit comedones, suppress the growth of Propionibacterium signaling [13]. Elevated insulin levels stimulate the secretion of acne or reduce sebaceous gland size and secretary activity. Some researchers have concluded by consumption of milk, stimulates proliferation of sebocytes, that genetic predisposition and hormonal influences play a more resulting in the development and progression of acne lesions. Estrogen is a healing therapies (such as acupuncture and massage), and other hormone that may reduce acne [9], [18-25]. There is a common traditional and folk remedies may follow similar mechanisms medical and lay belief that women experience perimenstrual in the treatment of acne.