By T. Roy. Virginia International University.

Areas of normal flow exhibit a relatively high level of tracer uptake 200mg ofloxacin with mastercard, while ischaemic regions present a relatively low uptake discount ofloxacin 400mg on-line. Regional coronary blood flow may be compared in conditions of rest, stress or pharmacologically induced vasodilation. In addition to evaluating relative regional blood flow these tracers are, therefore, also markers of myocardial viability. Myocardial perfusion scintigraphy may be performed using either single photon or positron emitting radionuclides. Among the commonly used single photon emitting 201 99m perfusion tracers are Tl and the various Tc labelled perfusion tracers (e. While having different physical and pharmaco- kinetic properties, these tracers have considerably overlapping clinical uses and will therefore be considered in parallel in this section. Clinical indications The clinical indications for myocardial perfusion tomography are summarized in Table 5. The presence of extensive ischaemia or myocardium at risk indicates the need for more invasive work-up, such as coronary angiography. Conversely, the absence of significant ischaemia or myocardium at risk generally rules out the need for intervention. Myocardial perfusion imaging can be performed in various settings: in patients with suspected coronary artery disease, after myocardial infarction or for the assessment of therapy. Myocardial perfusion imaging can also be used to evaluate the patho- logical significance of coronary lesions already detected by angiography. Angiographic coronary artery disease with a normal stress myocardial perfusion scan has little prognostic significance according to accumulated data. This helps clinicians to determine which patients to manage aggressively with invasive procedures and which ones to manage conservatively. As with detecting myocardium at risk, stratification using mycardial perfusion imaging can be done in various settings: in patients with suspected coronary artery disease, after myocardial infarction as well as before non- cardiac surgery (to determine the risk of perioperative cardiac events). The term ‘viable myocardium’, in its broadest sense, denotes any myocardium that is not infarcted. For the cardiologist, however, the search for myocardial viability is primarily a quest for myocardial hibernation. Myocardial hibernation is classically defined as chronic hypoperfusion and dysfunction that reverses after revascularization. It can be distinguished from myocardial stunning, which denotes acute but transient hypoperfusion and dysfunction, typically after a myocardial infarction in adjacent tissue that does not require intervention because it recovers spontaneously. It is now accepted, however, that the line separating hibernation from stunning is not as clear as was once thought. Various modifications to basic myocardial perfusion imaging protocols have been devised in order to distinguish hibernating, viable myocardium from non-viable, infarcted myocardium. These include late redistribution, re- injection imaging (both protocols using 201Tl) and nitrate augmented rest 201 99m imaging (using either Tl or Tc labelled agents). This may then be evaluated qualitatively by viewing the images in an endless loop cine-display, or quantitatively using commercially available software. The presence of global dilatation, thinned out walls, ventricular aneurysms and increased lung uptake are all suggestive of left ventricular failure. Radiopharmaceuticals A number of single photon emitting radiopharmaceuticals may be used for imaging myocardial perfusion. The three most commonly used at present are 201Tl and the 99mTc labelled tracers sestamibi and tetrofosmin. Thallium-201 also has gamma rays of 135 and 167 keV, which contribute little to the total image counts. The extraction fraction is linearly proportional to blood flow over a wide range of physiological flow levels, plateauing only at very high flow rates and logarithmically decreasing towards the very low flow range. Relative accumulation in the myocardium thus reflects relative regional perfusion. This radiotracer is characterized by redistribution in the myocardium, settling in equilibrium between the myocardial and blood pool concentrations. This makes 201Tl a marker of myocardial viability, which is perhaps its greatest advantage. Disadvantages Relatively long High hepatobiliary — half-life limits activity needs delay allowable dose. Protocols employing 99mTc-sestamibi involve post-injection waiting times of 45–90 min, to allow for adequate clearance of subdiaphragmatic activity. Technetium-99m-sestamibi is characterized by a minimal yet discernible amount of redistribution, which may sometimes be used as a marker of recoverable myocardium. Its main advantages are ease of preparation and faster hepatic clearance, allowing shorter post-injection waiting times of 20–30 min. Equipment (a) Cameras A single-crystal gamma camera is the basic piece of equipment required for myocardial perfusion imaging using both 201Tl and 99mTc agents. Planar imaging is not considered optimal for myocardial perfusion due to its lower sensitivity.

Such limiting generic ofloxacin 200 mg with amex, last no more than a few days purchase ofloxacin 200mg, do not couples face a number of important questions require treatment and should not be consid- and often encounter diffculties accessing the ered a ‘disorder’. This chapter reviews Postpartum depression – signifcant depres- what is known about severe mental illness in sive symptoms occur following more than relation to pregnancy and childbirth. Episodes of major depression of childbirth impacting their illness, diffcult at this time may cause signifcant emotional decisions regarding medication in pregnancy, impairment and lead to severe long-term and questions that women and their partners consequences. Duration Few days Weeks to months Weeks to months of the term ‘postpartum depression’ to refer Symptoms Depressed mood, Depressed mood, lack of Elated, irritable or depressed to all forms of psychological distress follow- Each will be considered in turn. This inappropri- What are the implications of pregnancy and hallucinations, rapidly ate usage not only trivializes severe episodes and childbirth on the psychiatric illness? Antipsychotic medication, future pregnancies, but also supports the inap- Although the link between severe psychiatric intervention exercise, computerized antidepressant medication, propriate labeling as a psychiatric disorder of a disorder and childbirth is well established, the cognitive behavioral therapy mood stabilizers (e. Most often may This chapter focuses on the care of women These surprising fndings have been attrib- be treated at home but severe with pre-existing severe mental illness remem- uted to methodological problems in terms of cases may need admission bering, of course, that many women experi- appropriate comparison groups. Although severe mental illness can the Danish psychiatric admission and birth be defned in various manners, here it includes registries demonstrated a ‘selection into par- women with a history of a psychotic illness enthood’ bias, in that women who become Postpartum psychosis – the most severe forms puerperium. Accordingly, the continuation such as schizophrenia or those with a severe mothers are a group at lower risk for psychi- of postpartum mood disorder have tradition- of a chronic psychosis such as schizophrenia mood disorder (bipolar disorder or severe atric disorders15 and studies taking this into ally been labeled as postpartum (or puerperal) would not be appropriately labeled as a post- 11 recurrent unipolar depression). The term ‘postpartum psycho- tum psychosis and depression are not sepa- In contrast, clear evidence supports a specifc include: sis’ is usually used to refer to the new onset, rate nosological entities, but merely repre- relationship to childbirth for episodes of severe although not necessarily the frst episode, of sent episodes of mood disorder triggered by • What are the implications of pregnancy affective psychosis and for bipolar disorder, a severe affective psychosis in the immediate childbirth. A previous with a history of schizophrenia, with Scandi- history of admission with bipolar disorder was navian register studies documenting increased 15 associated with an even larger increased risk postpartum admission rates15,23. For bipolar psychosis are at particularly high risk, with disorder, the risk is for the new onset of an epi- Figure 2 Increased risk of admission following delivery compared to at other times in a woman’s life for greater than 1 in 2 deliveries being affected18,19 sode of severe affective psychosis. Postpartum episodes on the bipo- women with schizophrenia may be admitted from reference 15 lar spectrum present a characteristic and close for different reasons, due to diffculties in par- temporal relationship to childbirth. For women or their partners who have suf- postpartum, with the majority being on days ety of psychiatric disorders, it is women with fered episodes of illness themselves, on the 1–320. Familial factors have been implicated in a history of bipolar disorder who are at a par- In addition to considering the effects of preg- other hand, it is still likely that the true risk the vulnerability to postpartum triggering of ticularly high risk of a severe recurrence. Table 2 gives the families with a history of severe mental illness approximate lifetime risk of mood disorder have another issue to consider when starting a for children of a parent with bipolar I disor- 1000 family. There are few data to give meaningful ric disorders run in families, and family, twin estimates for more distant family members, 900 and adoption studies have confrmed a high but available evidence suggests rates that are 800 levels of hereditability for many severe mental between those for frst degree relatives and 700 illnesses24. These fgures can be 570 600 rienced illness themselves or witnessed frst used as very approximate ‘order of magnitude’ 500 hand the suffering of a family member and be guides and, with appropriate caveats, can be concerned about passing on this risk to their used to provide information to women and 400 260 children; on occasion, the risk to offspring may their partners. Relationship to child Lifetime risk of bipolar I disorder Lifetime risk of major depression women studied had a severe form of unipolar Decisions regarding the fnal choice of pos- General population 0. It is disappointing that even for medications include teratogenicity, toxicity or sionals should not shirk their responsibility sure to two medications and the second drug a medication such as lithium that has been in withdrawal symptoms in the newborn as well to advise on appropriate options. Fully docu- may not have the effcacy of the original; and, use for over half a century, the sum total of the as the less certain risks of long-term devel- menting the nature and extent of any discus- fnally, continuing the current medication with world literature is not even 200 prospective opmental and cognitive problems in children sion is clearly important. Weighed When it comes to the decision about which Clearly, there are no easy answers, and again the situation is certainly better for medications against these risks, however, are the risks of medication to use, it is important to consider a full and individualized risk–beneft analysis used in psychiatry and additionally used in the untreated psychiatric disorders, including the drugs with the best evidence of reproduc- is important and should be meticulously doc- treatment of epilepsy, but there are potentially risk of a severe recurrence of illness. However, an individual woman’s umented in the patient record which should important differences in how medications are of studies implicate psychiatric disorder as history of response to various medications also state that the analysis had been accepted having important consequences on pregnancy, prescribed in other disorders, for example in 25 is clearly of vital importance. Rather, it is more lar history, additional factors that increase risk women with unipolar and/or bipolar disorder appropriate to deal in general principles that Inadvertent conception on medication include having experienced a previous episode who discontinue medication in order to con- should guide care. In a naturalistic study of 89 women with bipolar In an ideal world, all women with a history of and having a frst degree relative who has expe- severe mental illness would seek advice on a rienced an episode of postpartum psychosis18. In addition, should be asked about the above risk factors clearly carry a higher risk than others, sodium recurrence risk has been described in women the regularly estimated 50% of pregnancies and protocols should be put in place to ensure valproate being a prime example, each deci- with unipolar depression. Of 201 euthymic that are unplanned may even be higher in that women at potential risk receive a formal sion should involve consideration of a complex women with a history of major mental disor- women with severe mental illness. Therefore, patients with a Another major consideration is how to illness, pregnancy raises a number of diff- the importance of seeking help if contemplat- history of mental illness who might become cult issues. Severe recurrences are common in determine what level of information women ing pregnancy (or if unexpectedly becoming pregnant are well advised to supplement as a relationship to childbirth, and for women with want or are able to assimilate. Many fessionals need to be sensitive to differences of pregnancies are unplanned, all women with For women at risk, perhaps the most impor- medications used to keep women well are of between individual women and, wherever pos- childbearing potential merit thorough consid- tant aspect of management is to maintain known or potential teratogenicity, but stop- sible, individualize the information as well as eration of potential pregnancy when making close contact with their health care profession- ping medication may be associated with a very the manner in which it is delivered. The same data, nition that, due to its particular teratogenic other avoidable factors that may increase risk that these are issues that must be discussed delivered in a variety of manners, can confer and developmental effects, sodium valproate with all women with reproductive potential. Health care profes- Clearly, the earlier potential pregnancy is should not be used in women in their repro- example, and paying attention to sleep pat- sionals must be aware of their own biases and considered the better; many months or even ductive years if it can be avoided30. No universal recommendations exists for the use of lithium in this context , Information should be provided in a user- women in the preconception, antenatal and can be made, and the decision ultimately must but the few studies conducted have been open friendly manner. Stopping and retrospective, and there are practical prob- given in absolute rather than relative terms medication should always be a carefully con- lems with obtaining therapeutic levels quickly with a uniform denominator30. Why Mothers Die, It is easy to focus exclusively on medication First, it is important to consider the strength feelings with her partner, friends and family. Adv Psychiatr of hospitalization for postpartum psychotic and Treat 2009; in press bipolar episodes in women with and without prior prepregnancy or prenatal psychiatric hos- 12.

In a review of 176 pregnancies during be handled in accordance with the principles signs and symptoms suggestive of tumor pro- 4 malformations in pregnancies during which which quinagolide had been used for a median mentioned above for microprolactinomas buy discount ofloxacin 400mg. In such instances discount 400 mg ofloxacin mastercard, reinstitution, and newer compounds like cab- apy should not be instituted in women with a usually increase further after that period9. Experience regarding prolactinomas in pregnancy radiotherapy is considered harmful by increas- patient may be treated with dopamine ago- its use in pregnant women with prolactinoma ing the risk of hypopituitarism, it is not gen- nists in an attempt to reduce the size. In experimental models Microprolactinomas erally recommended in an attempt to control of pregnancy, cabergoline was not found to be therapy is insuffcient, transsphenoidal tumor tumor growth. Analyses of cabergoline-induced No clinical trials have compared the outcomes removal (preferably in the second trimester), may be continuation of the dopamine agonist gestations in humans revealed no increases in of women with microprolactinomas who have or early delivery in the third trimester may be treatment throughout the gestational period19. Figure 1 provides an algorithm for pregnancy-associated problems such as mis- been treated with dopamine agonists dur- Such an approach does not seem to pose a carriage and fetal malformations12. An may be required to achieve this goal (25– cal hypothyroidism in this same age group is untreated hypothyroidism, but not in those 39 important issue to be addressed is whether 325μg/day). The main cause The thyroid status should be closely moni- a pregnant woman during late pregnancy of hypothyroidism during pregnancy is auto- appropriate treatment of hypothyroidism and tored as autoimmune thyroiditis increases the whose severe hypothyroidism has previously immune thyroiditis, particularly in iodine- normalization of thyroid function in women risk of development of postpartum thyroiditis. This process is appropriate approach at this stage is debat- the world, however, the commonest cause is also valid for patients who cannot spontane- able, and most obstetricians would hesitate to iodine defciency26. Iron compounds are commonly used miscarriage, anemia, pre-eclampsia, placental are also compatible with the normal physi- abruption and preterm delivery30,31. The inci- Treatment of hypothyroidism in pregnant women, and their interference ological changes of pregnancy, identifcation of with intestinal T4 absorption may also worsen dence of postpartum hemorrhage and risk of patients with new-onset hyperthyroidism may 23 newborn acute respiratory distress syndrome Before conception, patients with known hypothyroidism during pregnancy. Since resin triio- be used, although there is no direct evidence the risk for miscarriage and preterm delivery dothyronine (T3) uptake is normally decreased in favor of this approach27. This occurs complications, untreated hypothyroidism may may also be based on the underlying cause of ability to cross the placental barrier and bind primarily due to a lack of capability on the part also be implicated in impaired fetal neuro- hypothyroidism. The result is of the affected thyroid gland to increase its development, particularly when hypothyroid- thyroiditis require less dose augmentation neonatal Graves’ disease causing hyperthy- secretory reserve to overcome the increased ism is present in early pregnancy27. Graves’ disease, gestational trophoblastic dis- thyroidism also tends to evolve into clinically cognitive and intellectual function in the off- As patients may be diagnosed initially dur- ease, toxic multinodular or uninodular goiter, overt disease by the same mechanism27. Clin Endocrinol (Oxf) 2006;65:265–73 The importance of timely diagnosis and treat- should be seen after 2–4 weeks for reassess- angiogenesis and genetics. A comparative review of the toler- The beta blocker drug propranolol should be stillbirth, preterm delivery, pre-eclampsia cross-sectional changes in plasma levels of ability profles of dopamine agonists in the 40 used with great caution to control adrenergic and intrauterine growth retardation. Obstet Gynecol studies should not be ordered in an attempt to fetal thyroid destruction, and defnite therapy 1985;312:1364–70 1983;62:425–9 should be postponed until after parturition23. Maternal hypothyroidism: recogni- reduction in the dosage and even discontinu- erable that macroadenomas be cured before tionship between maternal prolactin levels tion and management. Treatment of hyperthyroidism the treatment of hyperprolactinemic amen- the community: a twenty-year follow-up of Since untreated hypothyroidism may decrease orrhea. At high doses, however, both associated with increased risk of spontaneous nancy outcome after cabergoline treatment roid disease: further developments in our may pass the placenta and affect fetal thyroidal abortion. Mater- ment in euthyroid pregnant women with nal hypothyroidism in early and late gesta- autoimmune thyroid disease: effects on tion: effects on neonatal and obstetric out- obstetrical complications. Maternal hypothyroxi- Nat Clin Pract Endocrinol Metab 2007;3:470–8 84 7 Autoimmune and connective tissue disorders Anwar Nassar, Imad Uthman and Munther Khamashta Pregnant women with autoimmune rheumatic 1000 women1. Although once high risk of maternal disease fares, adverse considered a contraindication to pregnancy, fetal outcomes and potential drug terato- advances in disease management and perinatal genic effects, making the management of monitoring now make pregnancy outcome in these women particularly challenging. Nonethe- however, these risks can be minimized by less, signifcant risk of morbidity to both the appropriate timing of pregnancy and optimiza- mother and fetus still may occur. Prior treatment with outcome in women with chronic medical ill- alkylating agents such as cyclophosphamide is nesses, those with autoimmune rheumatic dis- one of the risk factors for infertility; however, eases being no exception. Women with severe renal nancy1,2,10,19,24 because this has been associated with these antibodies38 – to the most serious involvement are also at risk of deterioration in impairment (serum creatinine over 2. On the other hand, in the absence death secondary to end-stage renal or multi- strong risk factor for thrombotic events, fetal Drugs that can be continued during preg- 20,21 of active disease, hypertension, renal involve- system failure. Other risk factors include hyperten- pregnancy, as this medication decreases the should be undertaken by a multidisciplinary ated with better fetal and neonatal survival. In fact, its withdrawal is Although pulmonary hypertension is uncom- wide Inpatient Sample, a large database with ing throughout pregnancy in order to ensure frequently associated with subsequent fares in mon in lupus, it confers a high risk of maternal death when it occurs in pregnancy22,23. More recently, de Man and for conversion to safer pharmacologic regi- and congenital malformations including those prophylactic dose low molecular weight hep- associates, using a validated scoring system, mens. Preconceptional medical evaluation should occurs within the frst 6 months’ postpartum71 Since lefunomide may persist in the body for Whereas some authorities recommend dis- also include a precise review of the immuno- when almost all patients show signs of active up to 2 years77, the drug has to be discontinued continuation of these medications at least 3 logical status of the woman including lupus disease1. Similarly, in a How does pregnancy affect be associated with a risk of a major congenital national survey of 1425 pregnancies in women systemic sclerosis?

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