Stanley J. Kogan, MD

• Clinical Professor of Urology, Albert Einstein College of
• Medicine
• Chief, Pediatric Urology, Children? Hospital at Montefiore,
• Bronx, New York

Currently cholesterol za wysoki objawy order atorlip-20 20 mg with mastercard, there is no clear evidence that prenatal exposure of a vaccine with thiomersal has adverse effects cholesterol ratio wiki order 20 mg atorlip-20 visa, including neurodevelopmental disorders like autism cholesterol test superdrug best atorlip-20 20 mg. In a mass vaccination campaign in Zanzibar in 2009 where 196 pregnant women were inadvertently vaccinated (Hashim 2012) cholesterol test lipid profile generic atorlip-20 20 mg with mastercard, there were no differences in birth outcomes between the exposed and unexposed pregnancies gluten free cholesterol lowering foods 20 mg atorlip-20 order with mastercard. All people (including pregnant women) in areas where cholera is occurring, or has occurred, should observe five basic cholera prevention recommendations: (1) drink and use disinfected water; (2) wash your hands often; (3) use latrines; (4) clean up safely; and (5) cook or boil food, keep it covered, eat it hot and peel fruits and vegetables. Pregnant women who have to travel to an endemic region need to adhere rigorously to these precautions ("Boil it, cook it, peel it or forget it"). If compelling reasons are indicated, vaccination can be performed during pregnancy. There are no indications of embryotoxic properties in these vaccines, which have been extensively used for many decades (also in pregnant women). Large case control studies conducted in Hungary (Czeizel 1999) and Latin America (Silveira 1995), failed to detect any teratogenic effects of tetanus toxoid. Catindig (1996) noted that between 1980 and 1994 annual vaccinations increased in the Philippines by more than a factor of 10, and there was no increase in miscarriages. The suspicion by Heinonen (1977) linking an increased risk for pectus excavatum and club foot with tetanus toxoid has not been confirmed and appears to be anecdotal. If necessary, tetanus vaccinations should be refreshed during pregnancy to prevent maternal disease and neonatal tetanus. Reports about tetanus neonatorum in countries with inadequate vaccine protection support the urgency of the vaccination; for example, China (incidence of tetanus neonatorum is 0. Generally, the basic immunization is completed during childhood; thereafter, every 10 years a booster should be given, even during pregnancy. If protection is inadequate, a pregnant woman should be vaccinated against tetanus (and diphtheria). It is possible that after vaccination in the third trimester, maternal antibodies may cross the placenta and protect the infant from potentially life-threatening infections (Glezen 1999); corresponding antibodies have been also detected 3 and 6 months postnatally in breast milk, when the vaccination had been given between gestational weeks 34 and 36. To date, no recommendations have been made to protect the newborn by vaccination during late pregnancy. There is limited information about the use of hepatitis B vaccine during pregnancy. About 300 pregnancies with vaccinations at various times have been studied, and there is no increased risk of adverse outcomes demonstrated (Sheffield 2011, Reddy 1994, Grosheide 1993, Levy 1991, Ayoola 1987). Almost 90% of the mothers who demonstrated seroconversion after vaccination during pregnancy, developed protective antibodies that could be demonstrated in the umbilical blood (Sheffield 2011, Ingardia 1999). Passive transfer of the antibodies occurred in most of the newborns, but they disappeared rapidly in the infants (Ingardia 1999, Reddy 1994, Ayoola 1987). There are no reports that demonstrate adverse effects of hepatitis B vaccine during the course of pregnancy; however, the data are limited. Systematic studies of the use of hepatitis A vaccine in pregnancy are not available. A small case series reports 29 pregnant women who were vaccinated with hepatitis A vaccine. In an abstract, 23 pregnancies exposed to hepatitis A vaccine did not indicate an increased risk in adverse outcomes (Wilson 2010). So far, there have been no adverse effects with the use of hepatitis A vaccine in pregnancy; however, data are limited. Pregnant women at risk of acquiring hepatitis are recommended to undergo a vaccination. However, results of such data collections have methodological flaws and are to be viewed with caution. An accidental vaccination carries no consequences, but booster injections should be given after completion of the pregnancy. It contains three influenza virus strains that are expected to affect individuals during the upcoming winter. Pregnant women are at an increased risk of serious illness, and complications from influenza can result in more frequent as well as longer hospitalizations for respiratory infections. This holds for both seasonal and pandemic influenza (Liu 2013, Beigi 2012, Mosby 2011). Vaccination against influenza provides satisfactory immunity in pregnant women and reduces the risk of respiratory complications. Studies during the last decades with thousands of women, which evaluated the safety of influenza vaccine just before, or during pregnancy, demonstrate no evidence of embryo- or fetotoxic effects of the vaccine (Bednarczyk 2012, Munoz 2012). In a retrospective cohort study of 8,690 vaccinated pregnant women (439 in the first trimester), there was no increase in major malformation rates. However, the well-known marked underreporting seen with such a method of collecting data diminishes the relevance and importance of this report. A case control study utilizing data from six health care organizations in the Vaccine Safety Datalink found no statistically significant increase in spontaneous abortion in the 4 weeks after 182 2. In a retrospective, observational cohort also using data from the Vaccine Safety Datalink sites, no increased risks for adverse obstetric events was observed (Kharbanda 2013). An investigation in Bangladesh noted 36% less respiratory illness with fever among 172 pregnant women vaccinated with inactivated influenza vaccine when compared to a control group of women. Also, the children of the vaccinated mothers had 29% less infection up to 24 weeks postpartum. The reduction was even greater for children for lab-confirmed influenza infections, namely 63% (Zaman 2008). Maternal influenza immunization had a substantial protective effect in both mothers and in their young infants. The vaccine recommended for pregnant women differed among countries depending upon the perception of vaccine safety, efficacy, and operational issues related to vaccine production. There was an extensive monitoring of pregnancies which resulted in the development of substantial experience with these vaccines. Over 110,000 vaccinated pregnancies have been documented in numerous publications from Europe, United States, Asia and South America. The adverse events described were similar to those in the general population and were mainly mild. Vaccination during pregnancy did not result in an increased risk of adverse perinatal events or congenital malformations. Some studies even suggested a lower risk for preterm birth, low birth weight and fetal death. As relatively few women were vaccinated in the first trimester, the ability to assess the impact of vaccination on rates of congenital malformations is limited. Because the use of adjuvants in pregnancy had not been well studied in clinical trials, there were concerns about the safety during pregnancy. This could potentially result in placental dysfunction and a higher risk of preeclampsia, as a disturbed Th1/Th2 regulation has been discussed for some time as a cause of placental dysfunction (Mor 2010, Trowsdale 2006, Saito 2003). However, inadvertent use during pregnancy is no reason for termination of the pregnancy (Toback 2012). These results provide reassurance when offering influenza vaccination to all pregnant women. Vaccination of women who are or will be pregnant during the flu season is recommended. Infection with wildtype measles during pregnancy has been associated with miscarriage, prematurity and perinatal death in infected pregnancies. Cases of first trimester mumps followed by adverse fetal outcome have also been reported but are inconclusive. There have been no indications that measles or mumps infections during pregnancy cause birth defects in the child (Enders 2007). There is insufficient documented experience following the use of these vaccines during pregnancy. Some publications are focused on rubella vaccinations, but utilize data from rubella-measles combination vaccines. Thus, theoretical concerns for a risk using this live vaccine during pregnancy have not been confirmed. Although this finding is reassuring, it should be stated that the data are limited. Neither vaccine should be administered during pregnancy because, theoretically, fetal infection with the live attenuated vaccines might occur. While, generally, there is no indication to perform a measles and mumps vaccination during pregnancy, an accidental vaccination does not require any further intervention. It has been in use for decades and has not demonstrated fetotoxicity when given to pregnant women, primarily during the last trimester (Letson 1998). A study investigated 157 women who were vaccinated in the third trimester comparing them to a control group. It found that significantly higher levels of IgA and IgG, respectively, were present in the breast milk for up to three months, and in the serum of the newborns up to 6 months after birth (Shahid 2002). They are also given to infants and result in a better immune response than the polysaccharide vaccines. In the conjugated variety, parts of the bacterial wall are additionally bound to a protein. If clearly necessary, meningococcal vaccination may be conducted during pregnancy. It is being debated if the application of the acellular pertussis vaccine (aP) to the mother during pregnancy results in increased protection of the newborn through transmission of maternal antibodies. Because of the increase in incidences of pertussis in infants, immunization of pregnant women with pertussis vaccine is proposed (Leuridan 2013, Lindsey 2013, Bechini 2012). Systematic studies are lacking about the safety of Tdap during pregnancy; however, case series and reports do not indicate a risk. Pneumoccocal vaccination during pregnancy was proposed to be the way of preventing pneumococcal disease during the first month of life. However, experience with 280 pregnancies showed no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (Chaithongwongwatthana 2012). The formerly used oral polio vaccine (Sabin) contained live attenuated poliomyelitis viruses. Even with this live vaccine, no increased risk of malformations or miscarriages were observed when studies were conducted with mass vaccinations in Finland and Israel involving approximately 15,000 pregnant women (Harjulehto-Mervaala 1995, Ornoy 1993). Pregnancy is not a contraindication for a necessary polio vaccination with the inactivated vaccine. Case reports and series regarding the active and/or passive immunization with more than 330 pregnant women demonstrate no adverse effects (Huang 2013, Toovey 2007, Chutivongse 1995). Because rabies is a disease with a lethal outcome, a pregnant woman bitten by an animal suspected to be carrying rabies has to be immunized with vaccine and immunoglobulin. Other possible effects are growth restriction, hepatosplenomegaly and thrombocytopenia (Dontigny 2008). Because rubella vaccine contains live rubella virus, immunization is contraindicated shortly before and during pregnancy. A case report of a child with congenital cataract after maternal vaccination was not confirmed by another investigator (Fleet 1974). In another situation, the suspicion of rubella embryopathy after a maternal vaccination could be refuted by the demonstration of the presence of a wild-type virus (da Silva e Sб 2011). In a number of studies, data were analyzed covering more than 4,000 women who had been vaccinated from 3 months prior to conception and up to pregnancy. Data were collected from women in Germany, Sweden, England, Latin America, Iran and North America, some of them were already seropositive (Soares 2011, Nasiri 2009, Namaei 2008, Badilla 2007, Hamkar 2006, Enders 2005, Bar-Oz 2004). Also, a study from Iran did not detect clinical sequelae in the children from approximately 120 mothers who had no prior immunity (Hamkar 2006); in two other Iranian studies, 166 women were vaccinated shortly before or after conception. An investigation from Costa Rica (Badilla 2007) examined about 1,000 women who had been vaccinated during pregnancy or 1 month before. They did not find anomalies in regard to malformations, miscarriages, birth weight, and prematurity when comparing seronegative and seropositive mothers. In the majority of women who completed the follow-up, the immune status was unknown. During a mass vaccination campaign in Brazil, 2,332 susceptible women were vaccinated shortly before or during pregnancy. In summary, there has not been a single case of a rubella embryopathy as a result of a maternal vaccination, regardless if mothers were seronegative or had a preexisting (residual) immunity. A rubella vaccination should not be planned immediately before or during pregnancy. Current experiences argue against a risk of a rubella embryopathy as a result of vaccination. Thus, an accidental vaccination is no rationale for termination or invasive diagnostic steps. An individual decision should be made, if, as an exception, a seronegative woman with a high risk of exposure should be vaccinated during pregnancy. A study of 18 pregnant women who received the live vaccine during the first trimester (Mazzone 1994), and another report with 174 accidentally vaccinated women during pregnancy (Brooking 2003), did not reveal any specific abnormalities. Congenital varicella syndrome is characterized by cutaneous scarring in a dermatome distribution and/or hypoplasia of an extremity. Additional manifestations may include low birth weight, microcephaly, localized muscular atrophy, ocular anomalies, and neurological abnormalities (Mandelbrot 2012). Infants born to women who develop varicella within the period of 5 days before, to 2 days after, delivery are at risk of neonatal varicella, which may be severe. The manufacturer Merck collected 737 prospectively documented pregnancies, including 163 cases of live births of women who had been definitely seronegative prior to vaccination. The data revealed no evidence of a varicella embryopathy, higher malformation rates, or higher miscarriage rates.

Magnesium cholesterol ratio blood test order 20 mg atorlip-20, when used in higher doses or when kidney function is limited low cholesterol foods and recipes discount 20 mg atorlip-20 with mastercard, can cause marked muscle hypotonia in both mother and newborn cholesterol ratio in eggs purchase 20 mg atorlip-20 amex. Magnesium sulfate can be used for appropriate indications such as preeclampsia and eclampsia cholesterol test machine walgreens order atorlip-20 20 mg on-line. Its use as a tocolytic is questionable cholesterol test kit new zealand atorlip-20 20 mg buy on line, but it is recommended as a neuroprotective drug in case of preterm labor before 32 weeks of gestation. Atosiban competes with oxytocin for binding to oxytocin receptors in the myometrium, thus preventing the increase of free calcium in the cell. In a worldwide double-blind randomized trial of atosiban versus -agonists (Worldwide Atosiban versus -agonists Study Group 2001), both compounds resulted in similar rates of delivery within 48 hours and 7 days after the start of therapy. Atosiban, though, resulted in far fewer and particularly, less severe maternal side effects, and as a consequence substantially less discontinuations of therapy (Wing 2006). Atosiban is considered a safe drug in comparison with calcium antagonists and -mimetics. Adverse drug reactions were significantly lower as compared to betamimetics or calcium-channel blocking agents. However, given its favorable side-effect profile, oxytocin antagonists should be the first choice for women at increased risk, such as in multiple gestations and in preexisting maternal cardiovascular disease and diabetes. Atosiban appears to be safe when used properly, and can be considered for tocolysis during the preterm period and for reduction of excessive (induced) contractions at term. These agents can produce premature closure of the ductus arteriosus and impairment of renal function, with subsequent oligohydramnios. In short-term tocolysis (maximum 48 hours) before the thirty-second week of pregnancy this is seldom problematic, although the magnitude of the risks is still a subject of debate (for further detail, see also Chapter 2. Additional use of prostaglandin synthetase inhibitor in tocolysis is controversial, and should be reserved for treatment before 32 weeks of gestation. Ethyl alcohol has been used in the past for tocolysis, for its presumed inhibition of oxytocin release by the posterior pituitary gland. The harmful effects of alcohol on the development of the child are well known, and thus alcohol is an obsolete tocolytic (see Chapter 2. In a recent Cochrane review it was concluded that antibiotic treatment can eradicate bacterial vaginosis in pregnancy, however without significantly reducing the overall risk of (recurrent) preterm birth (Brocklehurst 2013). However, in two trials (only) in women with an abnormal vaginal flora (Nugent score <6) a reduction in preterm labor was found, and similarly in two trials, it was found that early clindamycin may reduce miscarriage. Overall there was no clear difference between oral and vaginal treatment, nor between metronidazole and clindamycin. Despite the presence of 21 trials of good quality, there remain many uncertainties regarding the treatment of bacterial vaginosis. The use of the Nugent score to identify an abnormal vaginal flora may identify women that will benefit from treatment, but further trials are needed. Antimycotics of first choice for local therapy of vaginal candidiasis are nystatin, clotrimazole, and miconazole. Vaginal douching with povidone iodine solutions increases maternal serum iodine levels and transiently alters maternal and fetal thyroid 410 2. To date, there is no indication that vaginally administered estrogens or disinfectants, such as dequalium, hexetidine, and policresulenum, have a teratogenic effect. However, it is good therapeutic practice to avoid obsolete and controversial agents. When treatment of bacterial vaginosis is indicated, oral antibiotics are the first choice (see details in Chapter 2. Vaginal administration of metronidazole or other antibiotics appears to be less effective. However, in one study of more than 700 children born to mothers who became pregnant in spite of the use of vaginal contraceptives, a slight increase in rate of malformations was observed (Jick 1981). Conception using vaginal spermicidals containing nonoxinol-9 has not been associated with an identifiable risk of birth defects. Tocolysis and delayed delivery versus emergency delivery in cases of non-reassuring fetal status during labor. Exposure to misoprostol and hormones during pregnancy and risk of congenital anomalies. A prospective randomized trial of acute tocolysis in term labour with atosiban or ritodrine. Adverse drug reactions to tocolytic treatment for preterm labour: a prospective cohort study. Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial. Pathophysiologie der Lungenцdementstehung bei der tokolytischen Therapie mit Fenoterol. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Calcium channel blockers for tocolysis: a review of their role and safety following reports of serious adverse events. Nifedipine and ritrodine in the management of preterm labor: a randomized multicenter trial. Effect of maintenance tocolysis with nifedipine in threatened preterm labour on perinatal outcome: a randomised controlled trial. Effect on normal vaginal flora of three intravaginal microbiocidal agents potentially active against human immunodeficiency virus type 1. Currently recommended oral regimens for ritodrine tocolysis result in extremely low plasma levels. Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse effects. Die Behandlung des Spдtabortes und der drohenden Frьhgeburt mit Thll65a in Kombination mit Isoptin. The localization and concentration of copper in the fallopian tube in women with or without an intrauterine contraceptive device. Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. Their regulation takes place on three levels, the hypothalamic level (primary releasing function), the stimulator level in the pituitary gland, and the glandular level in the respective organs. The secretion of the hormones is controlled via feedback mechanisms among the three levels or via the blood levels of the substance they are regulating. The classical hormones, antihormones and maternal disease of the endocrine system discussed in this chapter are distinguished from local tissue factors or mediators, which also include, among other substances, the prostaglandins (Chapter 2. They are used today as diagnostics for endometriosis, uterine myomas, in reproductive medicine, and for some hormone-dependent malignant illnesses. With the help of corticorelin, the corticotropic function of the anterior pituitary can be examined. The gonadorelin analog, triptorelin, is used in the course of assisted reproduction as well as in women with endometriosis and with uterine myomas. In a study comprising only six children, developmental problems such as attention deficits disorder, motor and language disturbances, were diagnosed in four children. Therapeutically, somatostatin analogs are used as hemostatics, with carcinoids and for reducing the effects of growth hormone in acromegaly. The treatment of pregnant women with octreotide was reported in more than 15 cases, without observation of any side effects. Most women were treated for acromegaly, and at least seven patients received the drug throughout pregnancy. One girl was examined regularly until she was six, with laboratory, neurological and clinical testing (Maffei 2010). Lanreotide, an analog of somatostatin, has been used since 2005 as a therapy for acromegaly. The therapy for acromegaly is an exception for which there is currently no general recommendation but also no contraindication for use in pregnancy. The release of pituitary hormones is controlled by hypothalamic releasing hormones. Indications for hormone treatment are: induction of ovulation and maintenance of the corpus luteum. The stimulation of ovulation with gonadotropins can lead to multiple pregnancies with 5­6% of the cases resulting in triplets. Two publications described one complex malformation and four neuroblastoma cases in the first year of life after gonadotropin stimulation (Mandel 1994, Litwin 1991). These findings were not confirmed by other studies, nor were other risks for the course of pregnancy described. Hence, there is no appreciable indication of damage when pituitary hormones are accidentally administered during pregnancy. Pegvisomant is a somatotropin receptor antagonist, which is used for acromegaly and for which several case reports are available. One such example is a case described by Brian (2007), of a woman who was treated during pregnancy with 15 mg per day of pegvisomant and gave birth to a healthy child. The medication known as thyrotropin alfa is used to detect the remains of the thyroid after a thyroidectomy. There is scarcely any indication for giving anterior pituitary hormones or their antagonists during pregnancy. The therapy for acromegaly is an exception for which there is currently no general recommendation. Should ophthalmological problems associated with macroprolactinomas, for example, arise in the course of the pregnancy, it is recommended to resume therapy. Bromocriptine, an ergot alkaloid derivative, is used for hyperprolactinemia (Chapter 4. A study of 2,587 pregnancies in which bromocriptine was given during the first weeks of pregnancy, gave no indication of teratogenic effects (Krupp 1987). Since most women stopped the therapy after discovering the pregnancy, the result confirms, at the same time, the harmlessness for the developing fetus of a continuing hyperprolactinemia. Cabergoline, a synthetic ergot alkaloid with a longer-lasting effectiveness is given for the same indications as bromocriptine but has a higher effectiveness and a more positive side-effect profile. Lebbe 2010, Ono 2010), even when treatment was continuous in some cases or had to be resumed in the course of the pregnancy. Up to now, there has been no indication of postnatal developmental disturbances (Lebbe 2010). A pediatrician has examined the children at regular intervals, in some cases up to the age of six (Ono 2010). Lisuride was used in a small retrospective study of 27 pregnancies to 17 hyperprolactinemic women. Most of them were treated with lisuride and there were 22 normal children, four induced abortions and one spontaneous abortion, possibly demonstrating that lisuride does not negatively affect pregnancies (Ventz 1996). Bromocriptine and cabergoline are the dopamine agonists of choice for hyperprolactinemia. This also applies to lisuride, metergoline and quinagolide for which a differentiated risk analysis is not yet possible due to limited experience in these products. Structurally, these octapeptide hormones are similar to the hypothalamic hormones. Desmopressin is used for treatment of already existing diabetes insipidus or diagnosed during pregnancy. Case reports on more than 50 pregnancies found no specific risk (Sбnchez-Luceros 2007, Siristatidis 2004, Ray 1998). There is no experience available in pregnancy for terlipressin, which is approved as an emergency medication for esophageal varices bleeding and which, in animal experiments, acts as an abortifacient. This is an important prerequisite for normal embryonic and fetal development as well as for an uncomplicated pregnancy. Before that, the placenta and embryo are exclusively dependent on the thyroid hormone supply via the mother. Pregnancy Metergoline can probably be evaluated similarly to the other prolactin antagonists. Experiences with the selective dopamine-D2-receptor agonist, quinagolide, which is not among the ergot alkaloids, are available for 10 pregnancies with healthy children. An additional 159 pregnancies collected by the manufacturer, where the mothers were treated for an average of 37 days of their pregnancy, had no indication of developmental toxic effects (cited in Webster 1996). Both the maternal as well as the fetal thyroid function are dependent on a sufficient iodine supply. In regions where iodine is in short supply, sufficient iodine should be assured even before a pregnancy. Since a supply through iodized salt, iodized foods and sea fish appears to be unreliable, 200­300 g of iodine should be substituted with tablets throughout the entire pregnancy. In populations with a sufficient iodine supply, chronic thyroiditis is the most common cause of thyroid hypoactivity. Also thyroid antibodies, without manifest hypothyroidism, increase the risk of spontaneous abortions (Gдrtner 2009) and premature births (Negro 2006). Depending on the severity and duration of (untreated) hypothyroidism during pregnancy, there may be impairment of neuropsychological development of the child. Pop (2003) studied the developmental outcome of 63 children born to mothers with low free thyroxin (fT4) during pregnancy compared to 62 children born to euthyroid mothers and found on the Bayley developmental scales an average reduction of 10 points on the mental scales, and of 8 points on the motor scales in the first and second year of life. Similarly, Li (2010) found delayed development at 25­30 months of age in offspring of women with subclinical hypothyroidism, hypothyroxinemia or elevated levels of thyroid peroxidase antibodies. In a study from the Netherlands (Henrichs 2010) maternal hypothyroxinemia was found to be a significant risk factor in the offspring for language and cognitive delay at 30 months. Haddow (1999) came to similar conclusions in a study on 60 seven to nine-year-old children. Many authors recommend screening for thyroid function disturbances, including thyroid antibody determinations before or, at least, after confirmation of a pregnancy.

Metals and trace element concentrations in breast milk of first time healthy mothers: a biological monitoring study cholesterol ldl hdl discount atorlip-20 20 mg buy on-line. Consequences for long-term neurological and cognitive development of the child lactation cholesterol test kit uk 20 mg atorlip-20 buy fast delivery. A critical review of methods for comparing estrogenic activity of endogenous and exogenous chemicals in human milk and infant formula grocery list cholesterol lowering foods order 20 mg atorlip-20. Analysis of the health risk of exposure to breast milk mercury in infants in Taiwan cholesterol goals chart purchase 20 mg atorlip-20 amex. High-level exposure to lithium cholesterol yeast rice order 20 mg atorlip-20 with amex, boron, cesium, and arsenic via drinking water in the Andes of northern Argentina. Current pediatric and maternal lead levels in blood and breast milk in Andean inhabitants of a lead-glazing enclave. Lead Concentrations in Maternal Blood and Breast Milk and Pediatric Blood of Andean Villagers: 2006 follow-up investigation. The mercury concentration in breast milk resulting from amalgam fillings and dietary habits. Levels of lead in breast milk and their relation to maternal blood and bone lead levels at one month postpartum. Collection and use of exposure data from human milk biomonitoring in the United States. Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. Development after exposure to polychlorinated biphenyls and dichlordiphenyldichlorethene transplacentally and through human milk. Polychlorinated biphenyls in the blood plasma: current exposure of the population in Germany. Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functions in young children. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. Association of prenatal exposure to an environmental contaminant with intellectual function in childhood. Meta-analysis of the relation between silicone breast implants and the risk of connective-tissue diseases. Effects of polychlorinated biphenyl/dioxin exposure and feeding type on infants mental and psychomotor development. Lactational transfer of presumed carcinogenic and teratogenic organochlorine compounds within the first six months of life in German. Environmental chemicals in human milk: a review of levels, infant exposures and health, and guidance for future research. Toxic and essential trace elements in human milk from Greek lactating women: association with dietary habits and other factors. Persistent organochlorine residues in human breast milk from Hanoi and Hochiminh City, Vietnam: contamination, accumulation kinetics and risk assessment for infants. Total and inorganic mercury in breast milk and blood in relation to fish consumption and amalgam fillings in lactating women. Epidemiology of hexachlorobenzene-induced porphyria in Turkey: clinical and laboratory follow-up after 25 years. Breastfeeding, exposure to organochlorine compounds, and neurodevelopment in infants. Changes in body burden of mercury, lead, arsenic cadmium and selenium in infants druing early lactation in comparison with placental transfer. Monitoring dioxins and furans in a population living near a hazardous waste incinerator: levels in breast milk. Rьckgang der Belastung von Humanmilch mit ausgewдhlten chlororganischen Verbindungen. Chlorinated hydrocarbons in fat tissue: analysis of residues in healthy children, tumor patients and malformed children. Rьckstдnde von Flammschutzmitteln in Frauenmilch aus Deutschland unter besonderer Berьcksichtigung von polybromierten Diphenylethern. Prenatal exposure to polychlorinated biphenyls and breastfeeding: opposing effects on auditory P300 latencies in 9-year-old Dutch children. Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood. Polychlorinated Dibenzo-Paradioxins and Dibenzofurans; Environmental Health Criteria 88. In addition, the reproduction effects of the drug, if any, have not been studied in animals. However, a placental perfusion study suggests that abciximab does not reach the fetus in clinically significant amounts. The primary risk, therefore, appears to be from maternal hemorrhage during drug administration. If this is adequately controlled, the benefits of the drug to the mother appear to far outweigh the unknown risks to the embryo­ fetus. Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications. It increases the risk of bleeding, especially when used with heparin and other anticoagulants or thrombolytics (1). No mutagenicity was observed with in vitro and in vivo tests, but long-term animal studies to detect carcinogenicity or adverse effects on fertility have not been conducted (1). Using an in vitro perfused human placenta, researchers found that only pharmaceutically insignificant amounts of abciximab could be detected in the fetal circuit. Minute amounts of abciximab were found on fetal platelets, but not on the endothelium or smooth muscle of fetal blood vessels, indicating that some transfer had taken place (2). Because her condition did not improve with aspirin, heparin, nitrates, or balloon angioplasty after an abciximab infusion was started, a stent was placed in the partially occluded left anterior descending coronary artery. Postoperatively, the woman was treated with ticlopidine, aspirin, and an unspecified -blocker. Two weeks later, she delivered a healthy baby boy vaginally, with no evidence of bleeding and a normal ductus arteriosus. Following placement of a stent, the woman again experienced chest pain and thrombus were discovered in three coronary arteries that were removed under coverage of abciximab (dose not specified) and intracoronary adenosine. The authors considered the anomalies relatively common with a benign prognosis (4). Because of the indications for abciximab, it is doubtful that such reports will be forthcoming. The very high molecular weight of the drug (about 48,000) suggests that it will not be excreted into milk in clinically significant amounts. Primary stent implantation for acute myocardial infarction during pregnancy: use of abciximab, ticlopidine, and aspirin. No reports describing its use in human pregnancy have been located, but such reports are unlikely because of the indication. Because of the risk of embryo and fetal harm, the drug is classified as contraindicated in pregnancy. It is indicated for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. Abiraterone is highly bound (>99%) to human plasma proteins, albumin, and 1-acid glycoprotein and the mean terminal half-life is 12 hours (1). Reproduction and carcinogenesis studies with abiraterone acetate in animals have not been conducted. However, neither abiraterone acetate nor abiraterone was mutagenic or clastogenic in multiple assays. In rats and monkeys, abiraterone caused atrophy, aspermia/hypospermia, and hyperplasia in the reproductive system at doses that were 1. These effects were consistent with the antiandrogenic pharmacologic action of the agent (1). It is not known if abiraterone acetate or its active metabolite abiraterone crosses the human placenta. The molecular weight of abiraterone acetate (about 392) and abiraterone (about 333) and the long terminal half-life of abiraterone suggest that both agents will cross to the embryo­fetus, but the high plasma protein binding of abiraterone might limit the exposure. The molecular weight of abiraterone acetate (about 392) and the active metabolite abiraterone (about 333), and the long terminal half-life of abiraterone (12 hours) suggest that the both agents will be excreted into breast milk. However, the high plasma protein binding (>99%) of abiraterone might limit the exposure. The effects of exposure to the drug on a nursing infant are unknown but, because of the potential for severe toxicity, breastfeeding is classified as contraindicated. The animal data suggest high risk, but the very limited human pregnancy experience prevents an assessment of the embryo­fetal risk. However, the use of ethanol (alcohol) in pregnancy is well known to cause dose-related developmental toxicity (see Ethanol). Even in the absence of obvious structural defects, alcohol use during gestation is associated with marked neurotoxicity in the offspring. Therefore, in pregnant women with alcohol dependency, the risk:benefit ratio may favor the use of acamprosate. Acamprosate is indicated to maintain abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. The mechanism of action is not completely understood, but acamprosate is thought to act differently than disulfiram, another agent in the class. Moreover, acamprosate and disulfiram have completely different chemical structures. The dose-related defects were hydronephrosis, malformed iris, retinal dysplasia, and retroesophageal subclavian artery. No carcinogenicity was observed in studies with rats, and no evidence of mutagenicity or clastogenicity was noted in several tests and assays. The molecular weight (about 400), lack of metabolism and protein binding, and long elimination half-life suggest that it will cross to the embryo and/or fetus. Vial, personal communication, Teratology Information Service, Lyon, France, 2010). The outcomes of these pregnancies included 2 spontaneous abortions, 3 elective abortions, 10 normal newborns (1 premature and 1 died at 1 month of age probably from sudden infant death syndrome), 1 newborn with minor facial anomalies, and a fetus and a newborn with major malformations. The fetus was electively aborted because of an omphalocele and found also to have microretrognathism, cleft palate, and a ventricular septal defect. Concomitant exposure to alcohol and other drugs occurred in several of the pregnancies. The molecular weight (about 400), lack of metabolism and protein binding, and prolonged elimination half-life (20­33 hours) suggest that the drug will be excreted in breast milk. However, alcohol is excreted into milk and is known to be a neurotoxin (see Ethanol). Thus, if a lactating woman requires acamprosate to refrain from drinking, the benefit to the nursing infant appears to outweigh the unknown risk from the drug. Acarbose is normally used in combination with oral hypoglycemic agents, and these hypoglycemic drugs might not be indicated for the pregnant diabetic. High maternal glucose levels, as may occur in diabetes mellitus, are closely associated with a number of maternal and fetal effects, including fetal structural anomalies if the hyperglycemia occurs early in gestation. To prevent this toxicity, the American College of Obstetricians and Gynecologists recommends that insulin be used for type 1 and type 2 diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (1,2). Less than 2% of a dose is absorbed as active drug in adults, but the systemic absorption of metabolites is much higher (approximately 34% of the dose) (3). Reproductive studies in rats found no evidence of impaired fertility or reproductive performance. A 1998 noninterventional observational cohort study described the outcomes of pregnancies in women who had been prescribed 1 or more of 34 newly marketed drugs by general practitioners in England (4). The outcomes of these pregnancies included two spontaneous abortions and three normal newborns (one premature) (4). In the oral group, 6% were changed to insulin because they were unable to tolerate acarbose (gastrointestinal complaints). A 35-year-old woman with several diseases (hypertension, diabetes mellitus, hypercholesterolemia, anxiety disorder, epilepsia, and morbid obesity) conceived while being treated with multiple drugs: rosiglitazone, gliclazide (a sulfonylurea), atorvastatin, spironolactone, hydrochlorothiazide, carbamazepine, thioridazine, amitriptyline, chlordiazepoxide, and pipenzolate bromide (an antispasmodic). As with all drugs, however, the safest course while taking acarbose is not to breastfeed until data on its safety during lactation are available. A comparison of oral acarbose and insulin in women with gestational diabetes mellitus (abstract). The drug undergoes extensive first-pass hepatic metabolism after oral administration (absolute bioavailability about 40%). The maximum dose in rabbits produced slight intrauterine growth restriction that was thought to be secondary to maternal toxicity (6). Newborn serum levels of acebutolol and the metabolite were <5­244 and 17­663 ng/mL, respectively (3). No human malformations attributable to acebutolol have been observed, but experience with the drug during the 1st trimester is lacking. In a study comparing three -blockers, the mean birth weight of 56 newborns was slightly lower than 38 pindolol-exposed infants but higher than 31 offspring of atenololtreated mothers (3160 vs. Growth restriction has been associated with -blockers and the weight reduction may have been drug induced. In a comparison of 20 pregnant women treated with either acebutolol or methyldopa for mild-to-moderate hypertension, no differences between the drugs were found for pregnancy duration, birth weight, Apgar scores, or placental weight (5). In addition, no evidence of bradycardia, hypoglycemia, or respiratory problems was found in the acebutolol-exposed newborns.

Alongside this cholesterol kefir order atorlip-20 20 mg with amex, there is the need for adequate information on the possible risks of exposure to chemicals in the workplace cholesterol levels risk calculator cheapest atorlip-20. These should include any information that exists on the reproductive and developmental toxicity of the chemical cholesterol levels us purchase genuine atorlip-20 on-line. However cholesterol levels for 15 year old best order for atorlip-20, in practice many workplaces require women to handle potentially toxic compounds and do not take into account the possibility that workers might already be pregnant average cholesterol hdl ratio atorlip-20 20 mg order. In addition, non-specific symptoms have to be considered when discussing the tolerability of workplace or household contaminants. If pregnant women complain of repeated symptoms in the workplace ­ such as headaches, emesis, vertigo ­ this should be taken seriously. Women may also have exaggerated responses to exposure simply because they are pregnant. With respect to awareness of an increased risk of birth defects from environmental pollution, birth defect monitoring systems would be of help. However, birth defect monitoring and surveillance systems seldom methodically measure environmental exposure. Only in the case of a cluster of defects with suggestions for pollution-related causation might such studies be performed. Absence of a change in the prevalence of birth defects in a population is not sufficient to exclude a (new) environmental developmental toxicant per se, since these monitoring systems are considered too insensitive. In the case of linkage of occupational exposures to reproductive hazards, the epidemiologist has to demonstrate that reproductive outcome is worse than expected when the mother or father has a specific occupational exposure, and that this is not due to confounders such as disease, maternal age, cigarette smoking, etc. Products such as degreasers, paint thinners, varnish removers, lacquers, silk-screening inks, and paints, also contain solvents. Exposure to one single solvent is rare; more frequently exposure is to mixed solvents by the inhalational and/or dermal routes. Hence, much of the epidemiology has been conducted on mixed or unspecified solvent exposure both at work and at home. Exposure to solvents has been associated with significant reductions in fertility in women working in agriculture (Sallmйn 2006), shoe manufacturing, dry cleaning, the metal industry (Sallmйn 1995, 2008), and the pharmaceutical industry (Attarchi 2012). Spontaneous abortions have also been reported to be significantly increased in solvent-exposed women working in various occupations and industries (see Taskinen 1990, for review). These include pharmaceutical manufacture (Attarchi 2012, Taskinen 1986), graphics and shoe manufacturing, (Lindbohm 1990), laboratories (Taskinen 1994), and semiconductor manufacture (reviewed by Lin 2008). In some of these occupations, exposure is to several solvents, and in some specifically to glycol ethers, toluene, xylene, or aliphatic hydrocarbon solvents. The evidence from the former is inconsistent but evidence from the latter shows an increase in the risk of small-for-gestational-age babies (see review by Ahmed 2007). In a meta-analysis of pregnancy outcome following maternal occupational exposure to organic solvents in the first trimester, it was concluded to be associated with a tendency towards an increased risk of spontaneous abortion (from five studies with 2899 subjects) and with a significantly increased risk of major malformations (from five studies with 7036 subjects) (McMartin 1998). An increased risk of major malformations and previous miscarriage was found in a Canadian study of women exposed occupationally to solvents in the first trimester through employment as factory workers, laboratory technicians, artists, graphic designers, and printing industry workers; importantly, maternal symptoms during exposure were predictive of an increased risk of malformations (Khattak 1999). An increased risk of major malformations was also reported in a cohort of Danish laboratory technicians with exposure to organic solvents (Zhu 2006). French studies on maternal occupational exposure to single organic solvents or to mixtures of solvents during the first trimester have reported a significantly increased risk of cleft lip with/without cleft palate (Chevrier 2006), and of major malformations, including oral clefts, urinary malformations and male genital malformations (Garlantйzec 2009). In both studies, the risk was related to the level of exposure and in the latter study the risk was associated with detection of metabolites of glycol ether and chlorinated solvents in maternal urine collected during early pregnancy (Cordier 2012). Previous studies have not found an association between exposure to glycol ethers and malformations (see Maldonado 2003 for review, Lin 2008). Some solvents are known to be neurotoxic and there have been a few studies on the neurodevelopment of children born to women with occupational exposure to solvents during pregnancy (Hjortebjerg 2012). Outcomes studied included general developmental neurobehavioral assessments, motor function, vision, language, attention, hyperactivity, and intelligence. Five of the six studies showed some deleterious effects (see Julvez 2009 for review), as has a more recent study (Pelй 2013). Non-occupational exposure to organic solvents in the form of paint fumes in the home environment have been studied in the large Danish National Birth Cohort, comprising 19,000 mothers, of which 45% reported exposure to paint fumes during pregnancy when interviewed around the 30th week. No relationship was found between exposure to paint fumes and birth weight or preterm birth (Sшrensen 2010); in the 7% reporting exposure in the first trimester, the risk of some types of malformations showed increased odds ratios, but the confidence intervals did not indicate statistical significance. Weak associations between solvent exposure in various occupations and reductions in male fertility have been reported but no specific solvents could be 2. Spontaneous abortions and congenital malformations in offspring among wives of men exposed to organic solvents have been studied in Finland. A significantly increased risk of spontaneous abortions but not malformations was found in Finland in wives of men exposed to organic solvents for 80 days before conception, but no significant effect was found in association with direct maternal exposure to organic solvents in the first trimester (Taskinen 1989). Male painters in the Netherlands exposed to organic solvents for 3 months before a conception had a significantly increased risk for malformations in their offspring compared to carpenters with little or no solvent exposure (Hooiveld 2006). An Egyptian study reported a significant increase in the risk of congenital malformations in the offspring of men occupationally exposed to solvents during the periconceptional period (El-Helaly 2011). A meta-analysis to assess the risks of spontaneous abortions and major malformations after paternal exposure to organic solvents concluded that paternal exposure was associated with an increased risk for neural tube defects, but not for spontaneous abortions (Logman 2005). In summary, occupational exposure to solvents, especially if associated with maternal toxicity, has been reported to cause reduced fertility and an increased risk of spontaneous abortion, fetal growth retardation, malformations and neurobehavioral effects in offspring. The effect of exposure of males on pregnancy outcomes in their partners is less clear. Acute exposure is not an indication for termination of pregnancy; neither are additional prenatal diagnostic tests required as long as the mother demonstrates no symptoms. If continuous and significant exposure has occurred, a detailed fetal ultrasound may be offered and fetal growth should be monitored. It is used in the manufacture of rayon textiles, cellophane, rubber and agricultural fumigants. Carbon disulfide-exposed women have been reported to have alterations in their menstrual cycles suggestive of hormonal abnormalities (Zhou, 1988). The results of Finnish studies suggested that female rayon workers exposed to carbon disulfide or wives of male rayon workers have an increased incidence of spontaneous abortion; however, no causal relationship with carbon disulfide exposures could be established (Hemminki 1982b, 1980). There is no clear evidence to indicate that maternal exposure is associated with an increased risk of fetal toxicity. In view of the possibility of fetal toxicity, exposure to carbon disulfide should be avoided in pregnancy. However, if the mother has had symptoms of toxicity and/or continuous exposure, she may be offered additional prenatal diagnostic measures ­. Chloroform (trichloromethane) Toxicology Chloroform is a widely used industrial and laboratory solvent. Interference with implantation and fetal growth retardation has been reported after exposure to chloroform in human pregnancy. Chloroform is also one of the prominent by-products from chlorination of drinking water (see Section 2. There are a small number of epidemiological studies on pregnancy outcomes following chloroform exposure, but they are difficult to interpret (Williams 1998, Reif 1996). Exposure in these studies was usually to chloroform and a varying number of other chemicals. In a study of 492 children of laboratory workers exposed to organic solvents during the first trimester of pregnancy, 148 were exposed to chloroform. The frequency of congenital anomalies was no greater than expected compared with the general population (Axelsson 1984). However, with multi-chemical exposure, establishing a cause-effect relationship is difficult. For spontaneous abortion, no increase in risk was found in 206 women exposed to chloroform in the pharmaceutical industry (Taskinen 1994), but an increased risk was found in women exposed to chloroform in biomedical research laboratories (Wennborg 2000). In cases where there is chronic exposure and/or severe maternal toxicity, a detailed fetal ultrasound should be offered and fetal growth monitored. The patient should be removed from exposure, and the workplace monitored for chloroform concentrations. Dichloromethane (methylene chloride) Toxicology the main uses of dichloromethane, a halogenated organic solvent, are as a solvent in paint removers, degreasing fluids, aerosol propellants and hair lacquers. As a consequence of its widespread use, many workers may be exposed for prolonged periods (Sullivan 1993). Dichloromethane is metabolized readily to carbon monoxide, which may have toxic effects on the developing fetal brain (see Chapter 2. There are three published studies on the effects of occupational exposure to dichloromethane in human pregnancy (Taskinen 1986, Axelsson 1984, Kurppa 1983). Data from these studies indicate that there was no overall increase in the incidence of congenital malformations or any 2. When there has been significant exposure this is not an indication for termination of pregnancy. However, if the mother has had symptoms of toxicity and/or continuous exposure, she may be offered additional prenatal diagnostic measures, such as a detailed fetal ultrasound. The patient should be removed from exposure, and the workplace monitored for dichloromethane concentrations. A number of studies have shown an increased risk for spontaneous abortion of about two-fold in women exposed to tetrachloroethylene in the laundry and dry-cleaning industry, and the risk is increased in more heavily exposed women (Doyle 1997, Windham 1991, Olsen 1990, Kyyrцnen 1989, Bosco 1987, Hemminki 1980). No increase in the incidence of low birth weight children or congenital malformations was reported in a Canadian study (McDonald 1987). None of the other studies were adequate to draw any conclusions about these outcomes. In summary, the data indicate an increased risk of spontaneous abortion associated with occupational exposure, but data are inadequate regarding other outcomes of pregnancy. Exposure to tetrachloroethylene should be avoided during pregnancy wherever possible. The patient should be removed from exposure, and the workplace monitored for tetracholorethylene concentrations. Toluene Toxicology Toluene (toluol, methylbenzene) is a widely used solvent in the paint, metal-cleaning products and adhesive applications (shoes) industries. However, there was no significant increase in the incidence of spontaneous abortion. Symptoms in the pregnant woman can be the first evidence of substantive exposure ­ dizziness, headaches and hallucinations can be one sign associated with the workplace or with use of the product. It is often difficult to separate the symptoms of pregnancy nausea and vomiting from toxic effects of the solvent. In either case, it will be necessary, if the symptoms persist, to remove the woman from the specific work area. The majority of information on toluene exposure in pregnancy comes from recreational use (solvent abuse). High exposures are associated with intrauterine growth retardation and with congenital anomalies (Wilkins-Haug 1997). In more than 30 cases of exposure to toluene via chronic recreational use to the point of "getting high," both maternal effects. Occupational exposure has been associated with reduced fertility (Plenge-Bцnig 1999) and spontaneous abortion (Ng 1992). A Canadian occupational exposure study on maternal solvent exposure and the occurrence of birth defects noted that most of the excess in defects was associated with toluene exposure (McDonald 1987). A review on the reproductive effect of toluene highlights that maternal solvent abuse, with intermittent high-level exposures, is more detrimental to fetal development than occupational exposures in which there is relatively constant low-level exposures (Hannigan 2010). The difficulty with occupational and environmental exposure to toluene compared with its abuse is similar to the use of alcohol (ethanol). Chronic abusive high levels resulting in persistent and acute symptoms, for both ethanol and toluene, result in impaired children. Chronic exposure in the workplace to levels resulting in substantive maternal symptoms is thought to place the offspring and mother at risk. Even if the levels of toluene are below the acceptable 8-hour threshold, the patient still may have to be moved to a non-solvent area because of enhanced sensitivity to odors and persistent and regular vomiting and nausea. It is recommended that the status of both mother and conceptus be more closely monitored throughout the pregnancy. Nevertheless, when there has been significant exposure this is not an indication for termination of pregnancy. However, if the mother has had symptoms of toxicity and/or continuous exposure, she may be offered additional prenatal diagnostic measures, such as a detailed fetal ultrasound including control of fetal growth. Formalin is a solution of formaldehyde in water, often with 10­15% methanol to prevent polymerization. One study reported that occupational exposure to formaldehyde was significantly associated with delayed conception (Taskinen 1999). In female hospital workers, some have reported no effect (Hemminki 1985, 1982a), while others have found a significant effect (Saurel-Cubizolles 1994). However, in addition to formaldehyde, such workers are also likely to have been exposed to other hazardous agents, such as anesthetics and ionizing radiation. Weak associations between spontaneous abortions and formaldehyde exposure have been reported in cosmetologists (John 1994), laboratory workers (Taskinen 1994), and wood workers (Taskinen 1999). No significant association was observed between maternal occupational exposure to formaldehyde during the first 3 months of pregnancy and congenital anomalies (Hemminki 1985, 1982a). A systematic review of epidemiological studies on occupational exposure to formaldehyde and reproduction found 16 studies relating to exposure of women. While recall bias and confounding could not be ruled out, the meta-analysis showed a significantly increased risk of spontaneous abortion from nine studies, and of all adverse pregnancy outcomes combined (spontaneous abortion, low birth weight, congenital malformation) from 12 studies (Duong 2011). Non-occupational exposure to formaldehyde through ambient air has also been studied. Higher ambient air exposures to formaldehyde tended to increase the risk of low birth weight and of unspecified congenital heart defects (Dulskiene 2005, Maroziene 2002). Exposure to chronic or high concentrations of formaldehyde and formalin should be avoided in pregnancy wherever possible. Exposure per se is not an indication for termination of pregnancy; as a rule, additional prenatal diagnostic tests are not required.

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