This is irrefutable but menopause yellow discharge purchase tamoxifen 20mg on line, unfortunately menopause 34 symptoms order 20mg tamoxifen mastercard, hypertension treatment and control rates worldwide are simply not as good as they could be women's health clinic uw order 20 mg tamoxifen amex. I recommend this guideline to clinicians and public health workers with the conviction that its contents will indeed contribute to the further prevention of premature morbidity and mortality women's health clinic on wright street tamoxifen 20mg visa. Chobanian has our deep gratitude for leading the effort to develop this report in such a timely manner women's health clinic spruce grove cheap tamoxifen 20 mg without prescription. Positive experiences pregnancy ring test tamoxifen 20 mg with visa, trust in the clinician, and empathy improve patient motivation and satisfaction. The awareness of hypertension among Americans has improved from a level of 51 percent in the period 19761980 to 70 percent in 19992000 (table 1). These changes have been associated with highly favorable trends in the morbidity and mortality attributed to hypertension. These benefits have occurred independent of gender, age, race, or socioeconomic status. Percent decline in age-adjusted mortality rates for stroke by gender and race: United States, 19702000 10 0 -10 P e r c e n t D ec l i n e -20 -30 -40 -50 -60 -70 1970 1975 1980 1985 Ye a r 1990 1995 White men White women Black men Black women Source: Prepared by Thom T, National Heart, Lung, and Blood Institute from Vital Statistics of the United States, National Center for Health Statistics. Percent decline in age-adjusted mortality rates for coronary heart disease by gender and race: United States, 19702000 10 0 -10 P e r c e n t D ec l i n e -20 -30 -40 -50 -60 -70 1970 1975 1980 1985 Ye a r 1990 1995 2000 White men White women Black men Black women Source: Prepared by Thom T, National Heart, Lung, and Blood Institute from Vital Statistics of the United States, National Center for Health Statistics. Hospital case-fatality rates for congestive heart failure for ages younger than 65 years and 65 years and older: United States, 19812000 14 I n H o s pi ta l M o rta l i t y (P e r c e n t) 12 10 8 6 4 2 0 1980 1985 1990 Ye a r 1995 2000 Ages <65 Ages 65+ Source: National Heart, Lung, and Blood Institute. Introduction 3 However, these improvements have not been extended to the total population. Current control rates for hypertension in the United States are clearly unacceptable. Hypertension is second only to diabetes as the most common antecedent for this condition (figure 7). Undiagnosed, untreated, and uncontrolled hypertension clearly places a substantial strain on the health care delivery system. Morbidity and Mortality: 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases. Hospitalization rates for congestive heart failure, ages 4564 years and 65 years and older: United States, 19712000 250 H o s pi ta l i z at i o n s / 1 0, 0 0 0 P o p u l at i o n 200 150 100 50 0 1970 1975 1980 1985 Ye a r 1990 1995 2000 Ages 4564 Ages 65+ Source: National Heart, Lung, and Blood Institute. Trends in incident rates of end-stage renal disease, by primary diagnosis (adjusted for age, gender, race) 350 R at e pe r M i l l i o n P o p u l at i o n 300 250 150 100 50 0 1992 1994 Ye a r 1996 1998 2000 All * these Diabetes* Hypertension* Glomerulonephritis Cystic kidney disease categories were treated as being mutually exclusive. The initial "Express" version, a succinct practical guide, was published in the May 21, 2003 issue of the Journal of the American Medical Association. To conduct this task, the Coordinating Committee is divided into four subcommittees: science base; long-range planning; professional, patient, and public education; and program organization. The subcommittees work together to review the hypertension scientific literature from clinical trials, epidemiology, and behavioral science. In many instances, the principal investigator of the larger studies has presented the information directly to the Coordinating Committee. It was published in an electronic format on May 14, 2003, and in print on May 21, 2003. The writing teams also met by teleconference and used electronic communications to develop the report. At its meetings, the Executive Committee used a modified nominal group process14 to identify and resolve issues. In addition, 33 national hypertension leaders reviewed and commented on the document. Methods 7 Lifetime Risk of Hypertension Hypertension is an increasingly important medical and public health issue. The prevalence of hypertension increases with advancing age to the point where more than half of people 6069 years of age and approximately three-fourths of those 70 years of age and older are affected. Framingham Heart Study investigators recently reported the lifetime risk of hypertension to be approximately 90 percent for men and women who were nonhypertensive at 55 or 65 years and survived to age 8085 (figure 8). Data for 65-year-old men in the 19521975 period is truncated at 15 years since there were few participants in this age category who were followed up beyond this time interval. Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospective studies. If the systolic and diastolic pressure readings for a subject were in different categories, the higher of the two categories was used. This revision reflects the fact that the approach to the management of the former two groups is similar (table 2). The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Rather, it is a designation chosen to identify individuals at high risk of developing hypertension, so that both patients and clinicians are alerted to this risk and encouraged to intervene and prevent or delay the disease from developing. The treatment goal for individuals with hypertension and no other compelling conditions is <140/90 mmHg (see Compelling Indications). The presence of each additional risk factor compounds the risk from hypertension as illustrated in figure 12. Management of these other risk factors is essential and should follow the established guidelines for controlling these coexisting problems that contribute to overall cardiovascular risk. The prevalence of systolic hypertension increases with age, and above 50 years of age, systolic hypertension represents the most common form of hypertension. A survey of primary care physicians indicated that three-fourths of them failed to initiate Figure 13. Results from the Third National Health and Nutrition Examination Survey, 19881991. Difference in coronary heart disease prediction between systolic and diastolic blood pressure as a function of age 1. A number of important causal factors for hypertension have been identified, including excess body weight; excess dietary sodium intake; reduced physical activity; inadequate intake of fruits, vegetables, and potassium; and excess alcohol intake. Systolic blood pressure distributions Because the lifetime risk of developing hypertension is very high (figure 8), a public health strategy, which complements the hypertension treatment strategy, is warranted. The probability of success increases as interventional strategies more aptly address the diversity of racial, ethnic, cultural, linguistic, religious, and social factors in the delivery of medical services. Community service organizations can promote the prevention of hypertension by providing culturally sensitive educational messages and lifestyle support services and by establishing cardiovascular risk factor screening and referral programs. Prevention of Hypertension: Public Health Challenges 17 C a l i b r at i o n, M a i n t e n a n c e, a n d U s e o f B lo o d P r e s s u r e D e v i c e s the potential of mercury spillage contaminating the environment has led to the decreased use or elimination of mercury in sphygmomanometers as well as in thermometers. The equipment- whether aneroid, mercury, or electronic-should be regularly inspected and validated. The operator should be trained and regularly retrained in the standardized technique, and the patient must be properly prepared and positioned. Caffeine, exercise, and smoking should be avoided for at least 30 minutes prior to measurement. An appropriately sized cuff (cuff bladder encircling at least 80 percent of the arm) should be used to ensure accuracy. Followup of patients with various stages of hypertension is recommended as shown in table 4. Recommendations for followup based on initial blood pressure measurements for adults without acute end organ damage Initial Blood Pressure (mmHg)* Followup Recommended Normal Prehypertension Stage 1 Hypertension Stage 2 Hypertension Recheck in 2 years Recheck in 1 year Confirm within 2 months Evaluate or refer to source of care within 1 month. Patient evaluation is made through medical history, physical examination, routine laboratory tests, and other diagnostic procedures. Data from epidemiological studies and clinical trials have demonstrated that elevations in resting heart rate and reduced heart-rate variability are associated with higher cardiovascular risk. In the Framingham Heart Study, an average resting heart rate of 83 beats per minute was associated with a substantially higher risk of death from a cardiovascular event than the risk associated with lower heart rate levels. Increased 20 the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Table 7. Screening tests for particular forms of identifiable hypertension are shown in table 8. Pheochromocytoma should be suspected in patients with labile hypertension or with paroxysms of hypertension accompanied by headache, palpitations, pallor, and perspiration. Examples of clues from the laboratory tests include unprovoked hypokalemia (primary aldosteronism), hypercalcemia (hyperparathyroidism), and elevated creatinine or abnormal Table 8. Appropriate investigations should be conducted when there is a high index of suspicion of an identifiable cause. These can generally be distinguished by the clinical setting and additional testing. For example, a renal ultrasound is useful in diagnosing polycystic kidney disease. While renal artery angiography remains the gold standard for identifying the anatomy of the renal artery, it is not recommend for diagnosis alone because of the risk associated with the procedure. At the time of intervention, an arteriogram will be performed using limited contrast to confirm the stenosis and identify the anatomy of the renal artery. Genetic association studies have identified polymorphisms in several candidate genes. Goals of Therapy the ultimate public health goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality. Consume a diet rich in fruits, vegetables, and lowfat dairy products with a reduced content of saturated and total fat. Engage in regular aerobic physical activity such as brisk walking (at least 30 min per day, most days of the week). The effects of implementing these modifications are dose and time dependent, and could be greater for some individuals. Tables 10 and 11 provide a list of the commonly used antihypertensive agents, and their usual dose range and frequency of administration. More than two-thirds of hypertensive individuals cannot be controlled on one drug and will require two or more antihypertensive agents selected from different drug classes. Oral antihypertensive drugs* Class Drug (Trade Name) Usual Dose Range in mg/Day 125500 12. Oral antihypertensive drugs* (continued) Class Drug (Trade Name) Usual Dose Range in mg/Day 12. Rationale for Recommendation of Thiazide-Type Diuretics as Preferred Initial Agent In trials comparing diuretics with other classes of antihypertensive agents, diuretics have been virtually unsurpassed in preventing the cardiovascular complications of hypertension. Higher doses have been shown to add little additional antihypertensive efficacy, and are associated with more hypokalemia and other adverse effects. Some reports have described an increased degree of sexual dysfunction when thiazide diuretics (particularly at high doses) are used. Thiazide diuretics are less expensive than other antihypertensive drugs, although as members of other classes of drugs have become available in generic form, their cost has been reduced. Selection of one of these other agents as initial therapy is recommended when a diuretic cannot be used or when a compelling indication is present that requires the use of a specific drug, as listed in table 12. If the initial drug selected is not tolerated or is contraindicated, then a drug from one of the other classes proven to reduce cardiovascular events should be substituted. Algorithm for treatment of hypertension the use of fixed-dose combinations may be more convenient and simplify the treatment regimen, and may cost less than the individual components prescribed separately. Use of generic drugs should be considered to reduce prescription costs, and the cost of separate prescription of multiple drugs available generically may be less than nongeneric, fixed-dose combinations. However, caution is advised in initiating therapy with multiple agents, particularly in some older persons and in those at risk for orthostatic hypotension, such as diabetics with autonomic dysfunction. More frequent visits will be necessary for patients with stage 2 hyper- tension or with complicating comorbid conditions. Serum potassium and creatinine should be monitored at least one to two times per year. Other cardiovascular risk factors should be monitored and treated to their respective goals, and tobacco avoidance must be promoted vigorously. The absence of a positive indication can signify a lack of information for a particular drug class. Furthermore, widespread use of combination therapy in clinical trials confounds interpretation of the effects of single drugs. Treatment should also include smoking cessation, management of diabetes, lipid lowering, antiplatelet agents, exercise training, and weight reduction in obese patients. However, there is no evidence that diuretics prevent progression of disease, and diuretics can also increase serum creatinine levels when used in excess. In most successful trials, systolic blood pressures were lowered to the range of 110130 mmHg. Of potential concern is the tendency for thiazide-type diuretics to worsen hyperglycemia, but this effect tended to be small and did not produce more cardiovascular events compared to the other drug classes. The incidence of ischemic or hemorrhagic stroke is reduced substantially by treatment of hypertension. No specific agent has been proven to be clearly superior to all others for stroke protection. There still are no large clinical studies upon which to base definitive recommendations. In African Americans, hypertension is more common, more severe, develops at an earlier age, and leads to more clinical sequelae than in age-matched non-Hispanic Whites. Unfortunately, sufficient numbers of Mexican Americans, other Hispanic Americans, Native Americans, or Asian/Pacific Islanders have not been included in most of the major clinical trials to allow reaching strong conclusions about their responses to individual antihypertensive therapies. The term "metabolic syndrome" describes a constellation of cardiovascular risk factors related to hypertension, Special Situations in Hypertension Management 39 abdominal obesity, dyslipidemia, and insulin resistance. The metabolic syndrome will likely increase further in the next several years, primarily because of the rapid increase in obesity.
Determining the optimal time for preterm delivery requires an evaluation of the risk to the mother and fetusofallowingthepregnancytocontinuecompared with the neonatal complications associated with pre termbirth menstrual kits for girls discount tamoxifen 20 mg overnight delivery. Thisisdonebymeasuringgrowthparameters breast cancer 5k nyc generic 20mg tamoxifen with mastercard,thebio physical profile (amniotic fluid volume women's health center hagerstown md generic tamoxifen 20 mg with mastercard, fetal move ment menstruation menopause discount tamoxifen 20 mg fast delivery, fetal tone menopause 54 discount tamoxifen 20 mg otc, fetal breathing movements menstrual 14 day to you tube cheap tamoxifen 20mg with amex, fetal heartactivity)andDopplerbloodflowvelocity(umbili calandmiddlecerebralartery). These measurements assist in deciding the optimal time for delivery of a growth restrictedfetus. Neonatalproblemsinclude: 9 Perinatal medicine Diabetes mellitus Women with insulindependent diabetes find it more difficulttomaintaingooddiabeticcontrolduringpreg nancy and have an increased insulin requirement. Poorlycontrolledmaternaldiabetesisassociatedwith polyhydramnios and preeclampsia, increased rate of earlyfetalloss,congenitalmalformationsandlateunex plained intrauterine death. With meticulous attention to diabetic control,theperinatalmortalityrateisnowonlyslightly greaterthaninnondiabetics. The incidence of macrosomia and its complications is similar to that of the insulin dependent diabetic mother, but the incidence of con genitalmalformationsisnotincreased. However,there areanincreasingnumberofmotherswithtype2non insulindependentdiabetes,associatedwiththeincrease in obesity in the population. Themacrosomia Summary Maternal diabetes · Meticulouscontrolpreconceptuallyandduring pregnancymarkedlyreducesfetalandneonatal morbidityandmortality. Treatmentwithantithyroiddrugsmay be necessary for several months until the condition resolves. The problem of establishing a link may be com pounded by a delay of months or years before any problems present. Severefetalthrombocyto penia places the fetus at risk of intracranial haemor rhage following birth trauma. Infants with severe thrombocytopenia or petechiae at birth should be given intravenous immunoglobulin. Maternal drugs affecting the fetus Relatively few drugs are known definitely to damage thefetus(Table9. While the teratogenicity of a drug may be recognisedifitcausesmalformationswhicharesevere and distinctive, as with limb shortening following thalidomide ingestion, milder and less distinctive abnormalitiesmaygounrecognised. Congenital infections Drug abuse Maternaldrugabusewithopiatesisassociatedwithan increased risk of prematurity and growth restriction. Infants of mothersabusingheroin,methadoneandotheropiates during pregnancy often show evidence of drug with drawal, with jitteriness, sneezing, yawning, poor feeding,vomiting,diarrhoea,weightlossandseizures duringthefirst2weeksoflife. Cocaineabuseisassoci ated with placental abruption and preterm delivery, but rarely with withdrawal in the infant, although it mayresultincerebralinfarction. Amphetamineabuse is also associated with gastrointestinal and cerebral in arction. Infants who develop significant features of drug withdrawalrequireadmissiontotheNeonatalUnitand treatment. Growth restriction Eye defects: cataracts microphthalmia retinitis Pneumonitis Hepatomegaly Jaundice Hepatitis Virus in urine Intracerebral calcification Hydrocephalus Microcephalus Deafness Heart defects: cardiomegaly patent ductus arteriosus Splenomegaly Rash: blueberry muffin or petechial Anaemia Neutropenia Thrombocytopenia Bone abnormalities Drugs given during labour Potential adverse effects to the fetus of drugs given duringlabourare: · Opioid analgesics/anaesthetic agents. Maycausesedation, · hypothermiaandhypotensioninthenewborn · Oxytocin and prostaglandin F2. Congenital infections 140 Intrauterineinfectionisusuallyfrommaternalprimary infection during pregnancy. Infected newborn infants are usually treated (pyrimethamineandsulfadiazine)for1year. About1%ofsus ceptible women will have a primary infection during pregnancy, and in about 40% of them the infant becomesinfected. Theinfantmayalsobecomeinfected following an episode of recurrent infection in the mother,butthisismuchlesslikelytodamagethefetus. Whenaninfantisinfected: inthefirsthalfofpregnancy(<20weeks),when thereisa<2%riskofthefetusdevelopingsevere scarringoftheskinandpossiblyocularand neurologicaldamageanddigitaldysplasia within5daysbeforeor2daysafterdelivery,when · thefetusisunprotectedbymaternalantibodies andtheviraldoseishigh. Infants born in the highrisk period should also receive zoster immune globulin and are oftenalsogivenaciclovirprophylactically. If a mother develops chickenpox shortly before or after delivery, the infant needs protection from infection. Thosespecifictocon genital syphilis include a characteristic rash on the solesofthefeetandhandsandbonelesions. Ifmothers withsyphilisidentifiedonantenatalscreeningarefully treated 1 month or more before delivery, the infant doesnotrequiretreatmentandhasanexcellentprog nosis. If there is any doubt about the adequacy of maternaltreatment,theinfantshouldbetreatedwith penicillin. Toxoplasmosis Acute infection with Toxoplasma gondii, a protozoan parasite, may result from the consumption of raw or undercookedmeatandfromcontactwiththefaecesof Adaptation to extrauterine life Inthefetus,thelungsarefilledwithfluid,andoxygen is supplied by the placenta. The blood vessels that supply and drain the lungs are constricted (high 1 2 Perinatal medicine 141 3 90%arenormalatbirthanddevelopnormally 5%haveclinicalfeaturesatbirth,suchas hepatosplenomegalyandpetechiae(Fig. Blood from the superior vena cava mainly flows into the right ventricle Inferior vena cava Ductus venosus Umbilical vein Descending aorta Umbilical arteries Oxygenation in the placenta Deoxygenated blood to the placenta via the umbilical arteries 142 pulmonaryvascularresistance),somostbloodfromthe right side of the heart bypasses the lungs and flows throughtheductusarteriosusintotheaorta,andsome flowsacrosstheforamenovale(Fig. Multi ple stimuli, including thermal, tactile and hormonal (withaparticularlydramaticincreaseincatecholamine levels), initiatebreathing. Lungexpansionisgenerated by intrathoracic negative pressure and a functional residualcapacityisestablished. Pulmonary expansion at birth is associated with a riseinoxygentension,andwithfallingpulmonaryvas cular resistance the pulmonary blood flow increases. Theflowof oxygenated blood through the ductus arteriosus causes physiological, and eventual anatomical, ductal closure. Itdoesnotnec essarily mean that the brain has been injured but asphyxia can lead to brain injury or death. A fetus Rapid breathing Irregular gasping Secondary apnoea Intermittent positive pressure ventilation Breaths Primary apnoea 200 Heart rate 160 120 80 40 Asphyxia Time Figure 9. Ifoxygendeprivation continues, primary apnoea is followed by irregular gaspingandthenasecondperiodofapnoea(second aryorterminalapnoea),whentheheartrateandblood pressure fall. If delivered at this stage, the infant will only recover if help with lung expansion is provided. The human fetus rarely experiences a continuous asphyxial insult, except after placental abruption or Table 9. More commonly, asphyxia, which occurs during labour and delivery is intermittent. Although birthasphyxiaisanimportantcauseoffailuretoestab lishbreathingrequiringresuscitationatbirth,thereare othercauses,includingbirthtrauma,maternalanalge sicoranaestheticagents,retainedlungfluid,preterm infant or a congenital malformation which interferes withbreathing. If there is any uncertainty about the adequacy of ventilation in an intubated baby, consider removing the tracheal tube, give mask ventilation and then reintubate. If at any time the heart rate drops below 60 beats/min, provided adequate breathing has been achieved, chest compressions should be given. If the response to ventilation and chest com pression remains inadequate, drugs should be given. Providing lung inflation, evidenced by good chest wall movement, is the key to successful neonatal resuscitation. Thebabycanbe handeddirectlytohisorhermother,andcoveredwith a warm towel to avoid becoming cold. However, a newborninfantwhodoesnotestablishnormalrespira tiondirectlywillneedtobetransferredtoaresuscita tion table for further assessment. There should be an overhead radiant heater and the infant shouldbedriedandpartiallycoveredandkeptwarm. Suctionofthemouthandnoseisnormallyunnecessary and vigorous suction of the back of the throat may provoke bradycardia from vagal stimulation. Iftheinfantdoesnotstarttobreathe,oriftheheart rate drops below 100 beats/min, airway positioning andlunginflationbybreathingbymaskventilationare started. Infants who also become acidotic may inhale thick meconium and develop meconium aspiration syndrome. Iftheinfantcriesatbirthandestab lishes regular respiration, no resuscitation is required. If respiration is not established, the larynx should be inspectedunderdirectvisionandanythickmeconium aspiratedbysuctioningwithalargeboresuctioncath eter, but if the infant becomes bradycardic, positive pressure ventilation will be needed despite the pres enceofmeconium. Is the baby breathing or crying, good heart rate (120160 beats/min, best assessed by listening with a stethoscope), good colour and muscle tone? Assess tone, breathing and heart rate 30s Always needed Start the clock Dry the baby Assess - tone, breathing, heart rate If gasping or not breathing: Open the airway Give 5 inflation breaths Consider SpO2 monitoring* 60s Re-assess If no increase in heart rate look for chest movement If chest not moving: Recheck head postion Consider 2-person airway control and other airway manoeuvres Repeat inflation breaths Consider SpO2 monitoring* Look for a response *Acceptable pre-ductal SpO2 2 min 60% 3 min 70% 4 min 80% 5 min 85% 10 min 90% Airway Breathing 5 inflation breaths Check airway and breathing Repeat inflation breaths Chest compressions Drugs Rarely needed If no increase in heart rate look for chest movement When the chest is moving: If heart rate is not detectable or slow (< 60 min-1) Start chest compressions3 compressions to each breath the inverted pyramid showing the relative frequency of procedures in neonatal resuscitation. Reassess heart rate every 30 s If heart rate is not detectable or slow (< 60 min-1) consider venous access and drugs Figure 9. If giving additional oxygen, use air/oxygen blender to titrate oxygen concentration with oxygen saturation on pulse oximeter. If heart rate not responding, check mask position, neck position, is jaw thrust needed, is circuit all right, ensure adequate chest movement. Call for help Intubation · Intubation and mechanical ventilation (g) are indicated if: mask ventilation is ineffective, tracheal suction needed to clear an obstructed airway, congenital upper airway abnormality, extreme prematurity-for giving surfactant. It should cover the mouth, nose and chin Correct Covers mouth, nose and chin but not eyes Incorrect Too large covers eyes and extends over chin Incorrect Too small does not cover nose and mouth completely (e) Mask ventilation (f) Two-person airway control (g) Tracheal intubation Pressurelimited air/oxygen Mask ventilation delivered with pressure-limited circuit via T-piece (as shown), Neopuff or self-inflating bag. One person holds the head in the correct position, applies jaw thrust and holds the mask in place. Apply pressure to lower third of sternum, just below imaginary line joining the nipples. Volume and drugs Consider drugs (k) if heart rate <60 beats/min in spite of adequate ventilation and chest compression, though evidence for their efficacy is lacking Rarely needed. Drugs should be given via an umbilical venous catheter, or, if not possible, via an intra-osseous needle. Giving standard doses of epinephrine (adrenaline) down the endotracheal tube does not appear to be effective, so drug dosage is increased for this route. A newborn baby who looks white and has poor skin and peripheral perfusion due to acidosis and peripheral vasoconstriction may have had acute blood loss. There may be a history of antepartum haemorrhage or acute twin-to-twin transfusion. Naloxone Infantsborntomotherswhohavereceivedopiateanal gesia within a few hours of delivery may occasionally developrespiratorydepression,whichcanbereversed by naloxone. It is only given if respiration continues to be depressed following initial resuscitation. Naloxone should not be given to babies of opiate abusing mothers as acute withdrawalsymptomsmaybeprecipitated. Resuscitation of the preterm infant Preterminfantsareparticularlyliabletohypothermia, and every effort must be made to keep them warm during resuscitation. Exces sive tissue oxygenation may cause tissue damage to the brain, lungs and eyes from oxygen free radicals. Ideally, an air/oxygen mixer should be used and any additionaloxygengiventitratedagainstoxygensatu ration. Very premature infants often develop respiratory dis tresssyndrome,andearlyendotrachealadministration of artificial surfactant may be indicated. An experienced paediatrician should beresponsibleforcounsellingtheparentsbeforedeliv ery,ifpossible,andleadthemanagementofthebaby afterbirth. Definitions Babies with a birthweight below the 10th centile for their gestational age are called small for gestational ageorsmallfordates(Fig. Failure to respond to resuscitation Thedecisiontostopresuscitationisalwaysdifficultand shouldbemadebyaseniorpaediatrician. Thelonger it takes a baby to respond to resuscitation, the less likely is survival. If there is no breathing or cardiac output after 10min of effective resuscitation, further effortsarelikelytobefruitlessandresuscitationshould be stopped. If prolonged resuscitation has been required,theinfantshouldbetransferredtotheneo natalunitforassessmentandmonitoring. Patterns of growth restriction Growth restriction in both the fetus and infant has traditionally been classified as symmetrical or asym metrical. In the more common asymmetrical growth restriction,theweightorabdominalcircumferencelies on a lower centile than that of the head. Thisformofgrowthrestrictionisassociatedwithutero placental dysfunction secondary to maternal pre eclampsia,multiplepregnancy,maternalsmokingorit maybeidiopathic. Largeforgestationalage infants are those above the 90thweightcentilefortheirgestation. Macrosomiais afeatureofinfantsofmotherswitheitherpermanent or gestational diabetes, or a baby with a congenital syndrome. The problems associated with being large for gestational ageare: Insymmetricalgrowthrestriction,theheadcircum ference is equally reduced. It suggests a prolonged period of poor intrauterine growth starting in early pregnancy(orthatthegestationalageisincorrect). It isusuallyduetoasmallbutnormalfetus,butmaybe due to a fetal chromosomal disorder or syndrome, a congenitalinfection,maternaldrugandalcoholabuse or a chronic medical condition or malnutrition. In practice, distinction between asymmetrical and symmetricalgrowthrestrictionoftencannotbemade. Toanswerthis,themidwife(orthepaediatri cianorobstetrician,ifpresent)willbrieflybutcarefully check that the baby is pink, breathing normally and hasnomajorabnormalities. Ifasignificantproblemis identified, an experienced paediatrician must explain the situation to the parents. If the baby is markedly preterm,smallorill,admissiontoaneonatalunitwill berequired. Babies are given vitamin K at birth to prevent haemorrhagic disease of the newborn unless parents will not give consent. The growth-restricted infant Afterbirth,theseinfantsareliableto: · · 148 hypothermiabecauseoftheirrelativelylarge surfacearea · hypoglycaemiafrompoorfatandglycogenstores detectcongenitalabnormalitiesnotalready identifiedatbirth,e. Breathing and chest wall movementareobserved the head circumferenceismeasuredwithapaper forsignsofrespiratorydistress. On palpating the abdomen, Thesagittalsutureisoften thelivernormallyextends separatedandthecoronal 12cmbelowthecostal suturesmaybeoverriding.
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Most metabolic models are based on enzyme conservation between their sequences and other more validated enzyme functional predictions and thus rely on statistical similarity between possible annotations and real annotations without direct evidence of their own function women's health issues in kenya purchase tamoxifen 20mg otc. This is time consuming women's health exercises at home generic 20mg tamoxifen fast delivery, expensive breast cancer 80 estrogen fed purchase tamoxifen 20 mg fast delivery, and requires both computational and biological aptitudes beyond the layperson women's health clinic ballarat order 20mg tamoxifen otc. They fail to consider intercellular interactions breast cancer financial assistance cheap tamoxifen 20mg otc, environmental reactions (including how cultures can change their environments) breast cancer jewelry charms generic tamoxifen 20 mg on line, and emergent behavior to form specific niches within communities. Therefore, any present predictions center on explicit model constraints, undervaluing the extensiveness of the evolved cellular apparatus and tending towards regurgitating their initial conditions. Reconstructions remain mere reflections of data, demonstrating a litany of possible pathways that cells can use to interact with their environments. The ideal scenario is to create a model that effectively predicts biological outcomes with more detail, cost-effectiveness, speed, and control than lent by experimental approaches, specifically with respect to defining possible phenotypes, characterizing cellular responses to perturbation, and visualizing internal 4 phenomena at high resolution. Progress toward more effective modeling solutions in more complicated hosts is contingent on addressing these three obstacles. It begins by evaluating experimental approaches to whole-scale data acquisition then progresses to selection of a ubiquitous, filamentous marine cyanobacterium that is a suitable model organism for metabolic modeling because of its metabolic properties, cellular similarity between cell types, and importance to the nitrogen, phosphorus, and carbon cycles (16). It presents a manually curated genome-scale metabolic model, extends it through computational techniques to describe a community, examines the effects of diverse conditions on metabolism, and concludes with an interrogation of the effects of the community on metabolic distribution in general. The overall outcome of this research is a three-step approach to applying computational models to biological systems, resulting in a biologically validated, integrative, and actionable modeling framework. The research extends each computational innovation directly to investigating carbon and nitrogen cycling in T. It evaluates how photosynthesis and nitrogen fixation function concurrently in two distinct cell types and they form a cooperative community. It establishes a diversifiable context in which cells can cooperate better by creating nuanced phenotypes within a filament. It examines the physical phenomena that govern behavior and how organisms respond at both individual and community levels opportunistically to diffusion gradients and light periods. Finally, it presents a preliminary natural metabolic circadian rhythm, using computational methods linked to biological experimentation to justify the existence of multiphasic growth even during routine, exponential, nutrient replete conditions. Its construction allows emergent behavior that describe cell diversification and environment utilization. It also introduces four ongoing subjects of research: computational improvements, biomass decoupling, how integration within a community and environment explain more extensive metabolic use, and addition of phosphorus metabolism into the model. To remedy this, researchers typically approach model organisms, or organisms that represent many processes of interest common to other species. From this angle and using the substantial number of tools available to the model organism, researchers have a foothold in approaching the new organism of interest. This chapter represents a similar approach, but instead of using experimental approaches to predict other biological behavior, it attempts to assess the state of experimental data in the model photosynthetic organism Chlamydomonas reinhardtii to act as a template for computational design. Therefore, we are employing a model organism to represent ideal computational outputs suitable for metabolic investigation in T. Many challenges face biofuels in their effort to replace petroleum fuels, but rational strain engineering of algae and photosynthetic organisms offers a great deal of promise. For decades, mutations and stress responses in photosynthetic microbiota were seen to 1 2 Reprinted with permission from Springer Publishing, Copyright 2016 (see Appendix E). This new equipment has created an exciting new frontier for high-throughput, predictable engineering of photosynthetically produced carbon-neutral biofuels. There are a number of alternative energy sources including wind, solar and hydroelectric which can be used to replace our dependence on fossil fuels for electricity; however, the ability to convert these energy sources to a form easily used for transportation is neither straightforward nor energy efficient. Biomass derived biofuels are particularly well-suited to displace some (or all) of our dependency on fossil fuels for the transportation sector because metabolites in the cell, such as starch or lipids, can easily be converted into fuels using current technologies. Advances in molecular biology and synthetic biology have allowed researchers to redesign metabolism and tailor-make molecules for fuel production (27-32). Another alternative, which has the potential to be carbon neutral, is the production of biofuels from photosynthetic microorganisms. Microalgae naturally accumulate lipids and starch or produce hydrogen when certain nutrients are depleted in the media (33-38), making them particularly attractive as sources of biofuels. With advances in analytical technologies, it is now possible to collect large amounts of data to characterize both model and non-model organisms. By comparing data 8 sets from different growth conditions, environmental stimuli, or genetic backgrounds, a more complete picture of how the cell responds to different stimuli can be gained. Its flexible metabolism is complemented by a complex structure reminiscent of higher order plants: it has multiple mitochondria, a chloroplast, flagella (42), and a cell wall of extension-like hydroxyproline-rich glycoproteins (43). There is also an emerging toolbox of molecular techniques for genetic manipulation of C. The availability of knock out libraries enables further research into gene/function relationships. Likewise, knowing the genes participating in cell walls and vacuolization can help C. While understanding of the cellular machinery is crucial to strain design, deconvolution of metabolism has been possibly the largest goal in rational biosynthetic design. Conclusions can be drawn from these experiments by using knowledge and connecting it to observed phenotypes; for 9 example, removing copper a cofactor in plastocyanin (50) resulted in a remodeling of the photosynthetic apparatus and identification of the Crd1 gene product as a response to oxygen deficiency (51). Carbon dioxide, sulfur deprivation, and other nutrient studies have demonstrated observable metabolic remodeling through starch accumulation, hydrogen accumulation, and various transcriptional changes, respectively (52-57). These stresses are now being studied at molecular levels to draw even deeper conclusions about stress response. In a lot of ways, the diversity of mutants and biological characterization afforded by the community has outpaced the sophistication of characterization techniques. Not only that, but the burgeoning molecular toolbox (59), including high-fidelity transgene expression (60), gene regulation manipulation through riboswitches (61), inducible promoters (60, 62), and chloroplast manipulation (63), can improve the experimental power in C. Genomics and transcriptomics can, then, be used to determine conserved behaviors across organisms, to infer transcript functions, or to determine gene function from phenotypes. Since genomics is the analysis of the whole information reservoir for an organism, it establishes the boundaries of the cellular landscape. Transcriptomics augments this analysis by cooperatively restricting the landscape through finding which parts of the genome are expressed and by elucidating complex gene interactions. By varying conditions, both changes and constancy in transcript levels can provide insight into regulatory pathways and the mechanisms by which fitness is maintained. Understanding this passage of information aids in determining and assessing the viability of genetic targets while establishing the boundaries of the cellular landscape. Manual annotation of sequenced genomes is not possible given how quickly genomes can be sequenced today. Genome browsers are available for a number of photosynthetic organisms through the Phytozome Genome Browser (78), which allows searching genomes for genes and supports further annotation efforts. Base pairs sequences on their own offer little insight into cell behavior; additional computation is used to find patterns between genomic and transcriptomic data. While earlier studies were conducted slowly by referencing primary literature, software tools (21, 79-81) in combination with genome and transcriptome databases (82-85) have significantly streamlined the process. Most tools operate by automatically patching (if necessary) and correlating sequences of highly conserved genetic regions. This allows examination of the actual regions expressed in the 11 genome and can be used to determine the structure of genes and possibly their function based on conserved sequences. These sequences can also be correlated across related strains to construct phylogenetic trees (86). Similarly to genomics and transcriptomics, proteomics begins with deconstruction into peptides via proteolytic digesting. Once done, chromatography, electrophoresis, or similar separations tactics are used to separate proteins. The peptide fragments can be sequenced using this method and analyzed by comparison to databases to identify concentrations and functions of the associated proteins. One drawback of this method is that degenerate peptides are indistinguishable with this technique (88). Computational and manual techniques can be used to link proteins to transcriptomics and genomics. This can be useful for several reasons: it identifies cell functions, protein conservation, and helps determine regulatory networks. In the first result, it builds on previous data from transcriptomics and genomics with either computational correlation (89) or more easily measured protein interactions. Furthermore, proteomics can be used in comparison to mutants or other organisms to determine conserved active sites and the effects of mutation (90). Metabolomics shows both conditional responses and the functional mechanisms in the cell which are not directly evident simply implied from protein concentrations and transcript levels. A symptom of this stress is the accumulation of energy storage and/or potential fuel molecules. Unfortunately, one undesirable side effect of nutrient depletion is reduced production of biomass (104). This in turn can be used to direct genome editing of other algal species more amenable to genetic manipulation or possessing traits more desirable for large scale production to improve the production of biofuels while maintaining normal growth rates and optimal cellular health. Reported changes in transcript abundance in biosynthetic pathways of triacylglycerols in Chlamydomonas reinhardtii. The sta6 mutant does not produce starch due to inactivation of the starch synthesis pathway indicated by. Cells starved of nitrogen can no longer synthesize new nucleic acids or proteins and therefore they are forced to slow (or cease) growth; however, to take advantage of ample carbon supply they divert their metabolism into storage of carbon as lipids and starches. Several transcriptomic, proteomic, and metabolomics studies exist for this condition in both wild type as well as the starchless mutant. Information gathered at each level may be used congruently to shed light on the regulatory mechanism for lipid accumulation without hindering overall biomass production. To determine the underlying causes of this fundamental response to nitrogen deprivation, Schmollinger et al. Each strain had different transcriptomes; however, amongst all three strains 27% of the total transcripts were shared. Unsurprisingly, all three strains increase transcripts for nitrogen transportation and assimilation; the proteins translated by the increased transcripts were also found to have increased concentrations. Additionally, proteins with low nitrogen content also increased in abundance during nitrogen starvation, while those of high nitrogen content decreased (106). Interestingly, of the 18 metabolites observed whose levels changed, amino acids phenylalanine, tryptophan, and aspartic acid as well as the amino acid degradation product putrescine were among those whose abundance decreased, possibly to serve as nitrogen sources for other metabolic needs (108). This mechanism of adaptation is responsible for the reduced biomass and cell arrest observed in cells starved of nitrogen. Thus, the regulatory mechanism by which these genes interact with those involved with lipid synthesis should be further investigated to identify specific genes that can be changed without causing cell death. Photosynthetic activity is also reduced in nitrogen starved cells, which limits their growth and ability to fix carbon. Enzymes and pigments required for photosynthesis have relatively high nitrogen content, thus, under nitrogen deplete conditions, the C. This limitation reduces the need to produce chloroplast ribosomes to synthesize these photosynthetic proteins and is apparent by the reduced chloroplast ribosome transcript levels (~75% reduction) observed by Schmollinger et al. Transcripts associated with chlorophyll degradation however remain constant after N-deprivation, therefore cells preferentially maintain chlorophyll despite the high nitrogen content (110). Additionally, transcripts for the Calvin-Benson cycle were reduced 2-8 fold as well as a 20% decrease in the corresponding proteins (106). From this, we see that cells subjected to nitrogen starvation are severely hampered in their ability to grow normally and re-organize their metabolism to maintain growth as much as possible. Thus, proteomic studies are necessary to determine the amount of protein actually resulting from these transcripts. Protein abundance levels of most enzymes involved with lipid synthesis either remained the same or decreased, indicating different levels of regulation involved with lipid synthesis. Of those enzymes involved with lipid synthesis whose associated transcript levels increased identified above (106, 109, 111), Wase et al. Such discrepancies between the transcript and protein abundance levels indicate that lipid synthesis is possibly regulated by variations in enzyme kinetics 17 at the protein level caused by substrate deviations at the metabolite level and/or post-translational modifications of those enzymes to promote lipid storage under nitrogen deplete conditions. Interestingly, when cells acclimated to phosphorous deplete conditions are exposed to sulfur deplete conditions, the cellular responses associated with sulfur deficiency become inhibited. Thus, the regulatory responses involved in sulfur deplete, phosphorous deplete, and possibly other nutrient deplete conditions are intimately dependent on one another (112). Additional sulfur-deplete studies indicate that the accumulation of lipids is a result of the conversion of phospholipids in the membranes into neutral lipids. Despite similar physiological responses between sulfur and phosphorous deplete conditions, the transcriptome of C. This observation is intriguing as phosphorous and sulfur deplete conditions exhibit a similar response as discussed above. Transcript fold changes of genes associated with enzymes involved in triacylglycerol synthesis of Chlamydomonas reinhardtii subjected to macronutrient deprivation. In general, most transcripts remain either unchanged or decrease when starved of nitrogen (-N), sulfur (-S), or phosphorus (-P). Although transcript levels were not analyzed, many predictions can be made about how cells accumulate lipids when heat stressed from the protein and metabolite variations observed. This decline in metabolic function illustrates that the cells undergo severe cell arrest, which may contribute to lipid accumulation. However, as indicated by the requirement for hydrocarbons and steam, this is not a carbon neutral process; in fact, it has been shown to have even more of a net negative impact than fossil fuels (116). Biological sources of hydrogen offer an advantage: the hydrogenase enzyme functions cooperatively with photosynthesis to convert protons into hydrogen gas as an electron sink instead of oxygen. In particular, acclimation to sulfur deplete and anoxic environments result in hydrogen gas being formed to compensate for cellular overprotonation and electron evolution. Analysis of these phenomena is crucial to eliminating the stress-induced cellular inefficiencies while maintaining the desired increase of biohydrogen. Knockout studies indicate that absence of hydrogenase genes in anoxia display a diversion of resources to relieving oxidative stress via other pathways such as succinate production (118) which can potentially provide targets for maintenance of cellular fitness during anoxia (Figure 2.
Thisisbecause: Moderate disability 31% Mild impairments 40% · thereismarkedphysiologicalreleaseof haemoglobinfromthebreakdownofredcells becauseofthehighHbconcentrationatbirth menopause effexor xr discount tamoxifen 20mg mastercard. It may occur when the level of unconjugated bilirubin exceeds the albumin bindingcapacityofbilirubinoftheblood menopause joint pain natural remedies purchase tamoxifen 20 mg online. The neurotoxic effects vary in severity from transient disturbance to severe damage and death women's health clinic kingston purchase tamoxifen 20mg without a prescription. In severecases women's health clinic paso robles tamoxifen 20 mg discount,thereisirritability women's health center in shelton ct buy 20mg tamoxifen overnight delivery,increasedmuscletone causingthebabytoliewithanarchedback(opisthot onos) women's health new zealand discount 20mg tamoxifen, seizures and coma. Infants who survive may develop choreoathetoid cerebral palsy (due to damagetothebasalganglia),learningdifficultiesand sensorineural deafness. Kernicterus used to be an important cause of brain damage in infants with severerhesushaemolyticdisease,buthasbecomerare since the introduction of prophylactic antiD Figure 10. Clinical evaluation Babiesbecomeclinicallyjaundicedwhenthebilirubin level reaches about 80µmol/L. Haemolytic disorders Rhesus haemolytic diseaseAffectedinfantsareusually identified antenatally and monitored and treated if necessary (see Ch. The birth of a severely affected infant,withanaemia,hydropsandhepatosplenomeg aly with rapidly developing severe jaundice, has become rare. Antibodies may develop to rhesus anti gens other than D and to the Kell and Duffy blood groups,buthaemolysisisusuallylesssevere. Jaundice <24 h of age Jaundice starting within 24h of birth usually results fromhaemolysis. Thisisparticularlyimportanttoiden tify as the bilirubin is unconjugated and can rise very rapidlyandreachextremelyhighlevels. Breast milk jaundice Jaundice is more common and more prolonged in breastfedinfants. The cause is multifactorial but may involve increasedenterohepaticcirculationofbilirubin. Dehydration In some infants, the jaundice is exacerbated if milk intake is poor from a delay in establishing breast feeding and the infant becomes dehydrated. Breast feeding should be continued, although the bilirubin levelwouldfallifitwereinterrupted. Jaundice at 24 h to 2 weeks of age Physiological jaundice Breast milk jaundice Infection. Jaundice at >2 weeks of age Unconjugated: Physiological or breast milk jaundice Infection (particularly urinary tract) Hypothyroidism Haemolytic anaemia. The causes and management of jaundice at >2 weeksofage(persistentneonataljaundice),(3weeksif preterm), are different and are considered separately below. The jaundice tends to start on the head and face and then spreads down the trunk and limbs. If the baby is clinically jaundiced, the bilirubin should be checked with a transcutaneous bilirubinmeterorbloodsample. Itiseasytounderes timate in AfroCaribbean, Asian and preterm babies, andalowthresholdshouldbeadoptedformeasuring the bilirubin of these infants. Inthiscase,thebilirubinisconjugatedandtheinfants have other abnormal clinical signs, such as growth restriction, hepatosplenomegaly and thrombocyto penicpurpura. Jaundice at 2 days to 2 weeks of age Physiological jaundice Most babies who become mildly or moderately jaun dicedduringthisperiodhavenounderlyingcauseand thebilirubinhasrisenastheinfantisadaptingtothe Rate of change the rate of rise tends to be linear until a plateau is reached, so serial measurements can be plotted on a chart and used to anticipate the need for treatment beforeitrisestoadangerouslevel. Clinical condition Infants who experience severe hypoxia, hypothermia or any serious illness may be more susceptible to damage from severe jaundice. Exchange transfusion Exchangetransfusionisrequiredifthebilirubinrisesto levels which are considered potentially dangerous. Blood is removed from the baby in small aliquots, (usuallyfromanarteriallineortheumbilicalvein)and replacedwithdonorblood(viaperipheralorumbilical vein). In rhesus haemolytic disease, it was found that kernicterus could be pre vented if the bilirubin was kept below 340µmol/L (20mg/dl). Management Poormilkintakeanddehydrationwillexacerbatejaun dice and should be corrected, but studies have failed to show that routinely supplementing breastfed infants with water or dextrose solution reduces jaun dice. Phototherapy is the most widely used therapy, withexchangetransfusionforseverecases. Phototherapy Light(wavelength450nm)fromthebluegreenband ofthevisiblespectrumconvertsunconjugatedbilirubin into a harmless watersoluble pigment excreted pre dominantly in the urine. It is delivered with an over head light source placed the optimal distance above the infant to achieve high irradiance. Although no longterm sequelae of phototherapy from overhead light have been reported, it is disruptive to normal nursing of the infant and should not be used indis criminately. Jaundice at >2 weeks of age Jaundice in babies more than 2 weeks old (3 weeks ifpreterm),iscalledpersistentorprolongedneonatal jaundice. The key feature is that it may be caused by biliary atresia, and it is important to diagnose Summary Assessment of neonatal jaundice Clinical assessment press skin to assess jaundice, which progresses from head to limbs, may underestimate if dark skin or preterm If clinically jaundiced check bilirubin with transcutaneous meter or blood sample Lower treatment threshold if preterm If <24 hours old likely to be haemolysis and potentially serious If > 2 weeks (3 weeks if preterm) persistent neonatal jaundice. However, in most infants with persistent neonatal jaundice,thehyperbilirubinaemiaisunconjugated,but thisneedstobeconfirmedonlaboratorytesting. Conjugated hyperbilirubinaemia (>25µmol/L) is sug gested by the baby passing dark urine and unpig mented pale stools. Respiratory distress in term infants Newborn infants with respiratory problems develop thefollowingsignsofrespiratorydistress: · · tachypnoea(>60breaths/min) labouredbreathing,withchestwallrecession (particularlysternalandsubcostalindrawing)and nasalflaring · expiratorygrunting · cyanosisifsevere. AchestXraywillberequired to help identify the cause, especially those causes which may need immediate treatment. It is rarely passed by preterm infants, and occurs increasinglythegreaterthegestationalage,affecting 2025%ofdeliveriesby42weeks. Meco nium is a lung irritant and results in both mechanical obstructionandachemicalpneumonitis,aswellaspre disposing to infection. Infantswith meconium aspiration may develop persistent pulmo naryhypertensionofthenewbornwhichmaymakeit difficulttoachieveadequateoxygenationdespitehigh pressure ventilation (see below for management). Transient tachypnoea of the newborn Thisisbyfarthecommonestcauseofrespiratorydis tressinterminfants. The condition usually settles within the first day of life but can take several days to resolve completely. Pneumonia Prolongedruptureofthemembranes,chorioamnioni this and low birthweight predispose to pneumonia. Infants with respiratory distress will usually require 172 investigationtoidentifyanyinfection. Pneumothoraces also occur sec ondary to meconium aspiration, respiratory distress syndromeorasacomplicationofventilation. Babies with bronchopulmonary dysplasia often have gastrooesophagealreflux,whichpredisposestoaspi ration. Persistent pulmonary hypertension of the newborn this lifethreatening condition is usually associated withbirthasphyxia,meconiumaspiration,septicaemia or respiratory distress syndrome. Asaresultofthehighpulmonary vascular resistance, there is righttoleft shunting withinthelungsandatatrialandductallevels. An urgent echocardiogram is required to establishthatthechilddoesnothavecongenitalheart disease. After stabilisation, the dia phragmatic hernia is repaired surgically, but in most infantswiththisconditionthemainproblemispulmo naryhypoplasiawherecompressionbytheherniated viscerathroughoutpregnancyhaspreventeddevelop mentofthelunginthefetus. The femoral arteries must be palpated in all infants with respiratory distress, as coarctation of the aortaandinterruptedaorticarchareimportantcauses ofheartfailureinnewborninfants. Infection the time of highest risk in childhood for acquiring a serious invasive bacterial infection is the neonatal period. In the newborn period, it usually presents with failure to respond to resuscitation or as respiratory distress. Once the Early-onset infection In earlyonset sepsis (<48h after birth), bacteria have ascendedfromthebirthcanalandinvadedtheamni oticfluid. In contrast, congenital viral infections and earlyonset infection with Listeria 1 2 3 Neonatal medicine 173 4 Box 10. Theriskofearlyonsetinfectionisincreasedifthere hasbeenprolongedorprematureruptureoftheamni otic membranes, and when chorioamnionitis is clini callyevidentsuchaswhenthemotherhasfeverduring labour. An acutephase reactant (Creactive protein) is helpful but takes 1224h to rise, so one normalresultdoesnotexcludeinfection,buttwocon secutive normal values are strong evidence against infection. Intravenous antibiotics are given to cover group B streptococci, Listeria monocytogenes and other Grampositive organisms (usually benzylpenicillin or amoxicillin), combined with cover forGramnegativeorganisms(usuallyanaminoglyco sidesuchasgentamicin). Use of prolonged or broadspectrum anti iotics predisposes to invasive b fungal infections. Neonatal meningitis, although uncommon, has a mortality of 2050%, with onethird of survivors having serious sequelae. Ifmeningitisisthoughtlikely, ampicillin or penicillin and a thirdgeneration cepha losporin. Some specific infections Group B streptococcal infection Around 1030% of pregnant women have faecal or vaginalcarriageofgroupBstreptococci. Theseverityoftheneonatalpresentationdependson the duration of the infection in utero. Up to half of infants born to mothers who carry groupBstreptococcusarecolonisedontheirmucous membranesorskin. In colonised mothers, risk factors for infection are preterm, prolonged rupture of membranes, maternal feverduringlabour(>38°C),maternalchorioamnionitis or previously infected infant. Prophylactic intrapar tum antibiotics given intravenously to the mother can prevent group B streptococcus infection in the newbornbaby. Nosocomially acquired infections are an inherent risk in a neonatal unit,andallstaffmustadherestrictlytoeffectivehand hygienemeasurestopreventcrossinfection. Inneona tal intensive care, the main sources of infection are indwelling central venous catheters for parenteral nutrition,invasiveprocedureswhichbreaktheprotec tivebarrieroftheskin,andtrachealtubes. Coagulase negative staphylococcus (Staphylococcus epidermidis) is the most common pathogen, but the range of Listeria monocytogenes infection Fetal or newborn Listeria infection is uncommon butserious. Theorganismistransmittedtothemother in food, such as unpasteurised milk, soft cheeses 174 and undercooked poultry. It causes a bacteraemia, often with mild, influenzalike illness in the mother, and passage to the fetus via the placenta. Maternal infection may cause spontaneous abortion, preterm deliveryorfetal/neonatalsepsis. Characteristicfeatures aremeconiumstainingoftheliquor,unusualinpreterm infants, a widespread rash, septicaemia, pneumonia andmeningitis. If the skin surrounding the umbilicus becomes inflamed, systemic antibiotics are indicated. This can be removed by applying silver nitrate while protecting the surrounding skin to avoid chemical burns,orbyapplyingaligaturearoundthebaseofthe exposedstump. Gram-negative infections Earlyonset infection is acquired in the same way as groupBstreptococcalinfection. Lateonsetinfectionis usually from infected central venous lines, but occa sionally from seeding to the circulation from the intestines. Theriskto aninfantborntoamotherwithaprimarygenitalinfec tion is high, about 40%, while the risk from recurrent maternalinfectionislessthan3%. Pres entationisatanytimeupto4weeksofage,withlocal ised herpetic lesions on the skin or eye, or with encephalitisordisseminateddisease. Mortalitydueto localiseddiseaseislow,but,evenwithaciclovirtreat ment, disseminated disease has a high mortality with considerablemorbidityafterencephalitis. Ifthemother is recognised as having primary disease or develops genitalherpeticlesionsatthetimeofdelivery,elective Caesarean section is indicated. Women with a history ofrecurrentgenitalinfectioncanbedeliveredvaginally as the risk of neonatal infection is low and maternal treatment before delivery minimises the presence of virusatdelivery. A more troublesome discharge with redness of the eye may be due to staphylococcal or streptococcal infection and can be treated with a topicalantibioticeyeointment,e. Purulent discharge with conjunctival injection and swellingoftheeyelidswithinthefirst48hoflifemay beduetogonococcalinfection. Thedischargeshould be Gramstained urgently, as well as cultured, and treatment started immediately, as permanent loss of vision can occur. Chlamydia trachomatis eye infection usually presents with a purulent discharge, together with swellingoftheeyelids(Fig. The vaccination course needs to be completed during infancyandantibodyresponsechecked. Hypoglycaemia Hypoglycaemiaisparticularlylikelyinthefirst24hof lifeinbabieswithintrauterinegrowthrestriction,who are preterm, born to mothers with diabetes mellitus, 1 2 3 Neonatal medicine 175 4 10 Neonatal medicine are largefordates, hypothermic, polycythaemic or ill foranyreason. Growthrestrictedandpreterminfants have poor glycogen stores, whereas the infants of a diabetic mother have sufficient glycogen stores, but hyperplasiaoftheisletcellsinthepancreascauseshigh insulin levels. Manybabiestoleratelowbloodglucose levels in the first few days of life, as they are able to utiliselactateandketonesasenergystores. In infants at increased risk of hypoglycaemia, blood glucose is regularly monitored at the bedside. The concentration of the intravenous dextrose may need to be increased from 10% to 15% or even 20%. High concentrationintravenousinfusionsofglucoseshould begivenviaacentralvenouscathetertoavoidextrava sationintothetissues,whichmaycauseskinnecrosis and reactive hypoglycaemia. If there is difficulty or delayinstartingtheinfusion,orasatisfactoryresponse is not achieved, glucagon or hydrocortisone can be given. Typically, there are repetitive, rhythmic (clonic) movements of the limbs whichpersistdespiterestraintandareoftenaccompa nied by eye movements and changes in respiration. Ongoingorrepeated seizures are treated with an anticonvulsant, although their efficacy in suppressing seizures is much poorer thaninolderchildren. Cerebral infarction (neonatal stroke) Infarction in the territory of the middle cerebral arterymaypresentwithseizuresat1248hinaterm infant.
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