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By J. Hengley. Concordia College, Moorhead Minnesota.

Treatm ent consists of anticoagulation with heparin and aspirin generic kamagra oral jelly 100 mg visa impotence world association. Lupus Versus Preeclampsia FIGURE 10-9 LUPUS FLARE-UP VERSUS PREECLAM PSIA In the second or third trim ester of pregnancy a clinical flare-up of lupus m ay be difficult to distinguish from preeclam psia kamagra oral jelly 100 mg discount erectile dysfunction treatment sydney. Treatm ent of a lupus flare-up m ight involve increased im m unosuppression, SLE PE whereas the appropriate treatm ent of preeclam psia is delivery. Thus, it is im portant to accurately distinguish these entities. Erythrocyte casts and hypocom - Hypertension + + plem entem ia are m ore likely to be a m anifestation of lupus, whereas Erythrocyte casts + - abnorm al liver function test results are seen in preeclam psia and not Azotemia + + usually in lupus. Low C3, C4 + - Abnormal liver function test results - +/- Low platelet count + +/- Low leukocyte count + - C— complement; minus sign— absent; plus sign— present; PE— preeclampsia; SLE— systemic lupus erythematosus. O verall, the outcom e in pregnancy is favorable when the serum creatinine level is less than 1. Anatomic, congenital Glomerulonephritis Interstitial nephritis Polycystic kidney disease Advanced Renal Disease Caused by Polycystic Kidney Disease FIGURE 10-11 POLYCYSTIC KIDNEY DISEASE Although advanced renal disease caused by polycystic kidney disease (PKD) usually devel- AND PREGNANCY ops after childbearing, wom en with this condition m ay have hypertension or m ild azotem ia. Pregnancy is associated with an increased incidence of asym ptom atic bacteriuria and urinary infection that m ay be Increased incidence of urinary tract infection m ore severe in wom en with PKD. The presence of m aternal hypertension has been shown Maternal hypertension associated with poor outcome to be associated with adverse pregnancy outcom es. Pregnancy has been reported to be associated with increased size and num ber of liver cysts owing to estrogen stim ulation. Extrarenal complications: subarachnoid hemorrhage, liver cysts W om en with intracranial aneurysm s m ay be at increased risk of subarachnoid hem orrhage during labor. M anagement of Chronic Renal Disease During Pregnancy FIGURE 10-12 MANAGEMENT OF CHRONIC RENAL M anagem ent of chronic renal disease during pregnancy is best DISEASE DURING PREGNANCY accom plished with a m ultidisciplinary team of specialists. Preconception counseling perm its the explanation of risks involved with pregnancy. Patients should understand the need for frequent Preconception counseling m onitoring of blood pressure and renal function. Protein restriction Multidisciplinary approach is not advisable during gestation. W hen renal function is im paired, m odest salt restriction Frequent monitoring of blood pressure (every 1–2 wk) and renal function (every mo) m ay help control blood pressure. Blood pressure should be m ain- Balanced diet (moderate sodium, protein) tained at a level at which the risk of maternal complications owing Maintain blood pressure at 120–140/80–90 mm Hg to elevated blood pressure is low. Patients should be m onitored Monitor for signs of preeclampsia closely for signs of preeclampsia, particularly in the third trimester. The usual RENAL DISEASE IN PREGNANCY causes are new-onset glom erulonephritis or interstitial nephritis, lupus nephritis, or acute renal failure. Rarely, obstructive uropathy develops as a result of stone disease or large m yom as that have Glomerulonephritis Interstitial nephritis increased in size during pregnancy. Lupus nephritis Obstructive uropathy Acute renal failure Investigation of the Cause of Renal Disease During Pregnancy FIGURE 10-14 RENAL EVALUATION Investigation of the cause of renal disease during pregnancy can be conducted with serolog- DURING PREGNANCY ic, functional, and ultrasonographic testing. Renal biopsy is rarely perform ed during gesta- tion. Renal biopsy usually is reserved for situations in which renal function suddenly deteri- orates without apparent cause or when sym ptom atic nephrotic syndrom e occurs, particular- Serology ly when azotem ia is present. Alm ost no role exists for renal biopsy after gestational week Function 32 because at this stage the fetus will likely be delivered, independent of biopsy results. Ultrasonography Biopsy: <32 wk Deteriorating function Morbid nephrotic syndrome New-Onset Azotemia, Proteinuria, and Hypertension Occurring in the Second Half of Pregnancy FIGURE 10-15 INTRINSIC RENAL DISEASE VERSUS PREECLAM PSIA N ew-onset azotem ia, proteinuria, and hypertension occurring in the second half of pregnancy should be distinguished from pre- eclam psia. M ost cases of preeclam psia are associated with only Renal disease Preeclampsia m ild azotem ia; significant azotem ia is m ore suggestive of renal dis- ease. Azotem ia in the absence of proteinuria or hypertension would Serum creatinine >1.

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In these patients cheap 100 mg kamagra oral jelly amex erectile dysfunction statistics uk, the re- Studies in cocaine abusers to assess DA release by the ductions in DA D2 receptors were significantly correlated DA terminal have been done using PET and the DA D2 with metabolic activity in prefrontal cortex purchase kamagra oral jelly 100mg with amex erectile dysfunction drugs sales, orbitofrontal radioligand [11C]raclopride. Studies to assess DA release cortex, and cingulate gyrus (34). Lower values for D2 recep- were performed with and without administration of MP, tors were associated with lower metabolism in orbitofrontal which is a drug that, like cocaine, blocks DAT. In humans, cortex, cingulate gyrus, and prefrontal cortex, a finding sug- the measures of MP-induced DA changes are reproducible gesting an association between DA activity and the function (42), and they are similar in magnitude to those induced of these frontal brain regions. The persistence of the de- by equivalent doses of cocaine (43). Studies comparing the creased D2 function raise the question of long-term cocaine- changes in [11C]raclopride binding between cocaine abusers induced changed versus preexisting DA system deficits that and control subjects showed that the response of cocaine could increase vulnerability to cocaine dependence. The 'high' Abnormalities in orbitofrontal cortex and cingulate gyrus induced by intravenous MP was also more intense in con- have also been reported for patients with obsessive-compul- trols than in cocaine abusers, whereas in cocaine abusers sive disorders (35), with whom cocaine abusers share the but not in controls, MP induced intense cocaine craving. In patients with ob- This finding indicates that cocaine-dependent patients re- sessive-compulsive disorders, this feature manifests itself in lease less DA in the striatum and have a blunted 'high' specific behavioral rituals, and in cocaine abusers, it mani- relative to controls when they are given MP. These results fests as an obsession to procure the drug and in the repetitive provide evidence that cocaine addiction does not imply an pattern of cocaine self-administration. In laboratory ani- enhanced pleasurable response nor is there a sensitized DA mals, destruction of the orbitofrontal cortex leads to the response to the drug. Rather, the reduced DA release and emergence of repetitive behaviors that cannot be easily ter- blunted 'high' are compatible with cross-tolerance between minated (36), and a similar syndrome can be generated by cocaine and intravenous MP. Thus, The marked decrease in DA brain function in the cocaine it has been postulated that DA-mediated dysregulation of abusers (reduction in DA D2 receptors, DA synthesis, and the orbitofrontal cortex and the anterior cingulate gyrus may release) may lead to a decrease in activation of DA-modu- Chapter 103: Application of Imaging Technologies in Drug Addiction 1481 lated reward circuits that are important in drive and motiva- Opioid System tion. Thus, one could postulate that the decreased in DA The endogenous opioid system has been implicated in the activity in cocaine abusers may make normal reinforcers reinforcing actions of cocaine and other addictive drugs. The decrease in DA function may also contribute oid binding was increased in several brain regions of the to the dysphoria and the anhedonia experienced by these cocaine addicts in proportion to the severity of cocaine crav- patients during cocaine withdrawal. Thus, strategies to en- ing experienced at the time. The up-regulation of -opioid hance DA brain function in cocaine abusers may help these receptor binding persisted after 4 weeks of detoxification. GABA System Alcohol Cocaine enhances DA brain activity, and DA signals are Imaging studies in patients with alcoholism have been done transferred by -aminobutyric acid (GABA)ergic pathways to measure CBF, brain glucose metabolism (baseline and (44). PET studies have shown DA D2 receptors, and DATs and serotonin transporters in significant reductions in striatal DA D2 receptors in cocaine brain. Because D2 receptors are predominantly located on GABA cells (45), reductions of these receptors suggest involvement of GABA pathways in cocaine abusers. Brain Metabolism and Cerebral Blood Flow The GABA system has been evaluated in cocaine abusers Most of the nonstructural imaging studies have been done with functional imaging techniques. These studies assessed to investigate brain metabolic and CBF changes in patients the brain regional responsivity to GABA stimulation in co- with chronic alcoholism with and without neurologic im- caine abusers and controls (46). Brain responsivity to GABA pairment (reviewed in refs. Patients with alco- stimulation was assessed by measuring the brain metabolic holism and Korsakoff encephalopathy showed decreased responses to lorazepam, a drug that facilitates GABA neuro- metabolism in prefrontal, parietal, and temporal cortices, transmission. Although plasma lorazepam concentration and patients with alcoholism and neurologic symptoms was significantly higher in controls that in drug abusers, other than Korsakoff encephalopathy showed decreased me- lorazepam-induced sleepiness in cocaine abusers was signifi- tabolism in frontal and parietal cortices. Studies in patients cantly more intense than in controls. Lorazepam reduced with alcoholism who have no evidence of neurologic impair- whole-brain metabolism, the decrements were greater in ment have also consistently shown evidence of frontal ab- drug abusers (21 3 %) than in controls (13 7 %), and normalities (reviewed in ref. Decrements in metabolism the differences were largest in striatum, thalamus, and pari- were most accentuated in the older patients with alcoholism etal cortex. Because lorazepam-induced sleepiness was corre- with longer histories of alcohol consumption. The degree lated with changes in thalamic metabolism, this finding sug- of brain metabolic recovery with detoxification was evalu- gests that the increased sedation in cocaine abusers results ated with PET in patients with alcoholism who were evalu- from the enhanced sensitivity of the thalamus to lorazepam.

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One of the developments in ECT practice in the 1990s old purchase 100 mg kamagra oral jelly with amex erectile dysfunction doctor in delhi. Although the virtual lack of TCA trials in these same patients before it is clear that the lower intensity RUL strategies have less coming to ECT purchase kamagra oral jelly 100mg erectile dysfunction and premature ejaculation underlying causes and available treatments. This is especially important because there acute amnesia side effects, this advantage is probably offset are some data to suggest that TCAs (i. Possibly, the addition of an antide­ dictors of QOL in severely depressed patients (56,57). There is a potential risk to stimulating the vagus nerve with subconvul­ PREVENTION OF RELAPSE AFTER ECT sive stimuli without adequate compensatory adrenergic dis­ charge from a seizure and the possibility of prolonged asys­ In general, patients who receive an acute course of ECT are tole. However, a controlled operative setting with cardiac either subsequently resistant or intolerant of antidepressant monitoring decreases the possibility of brief periods of medications. Patients diagnosed with psychotic depression bradycardia causing any significant risk for a majority of are particularly susceptible to relapse after an acute course patients. Two studies found a relapse rare of approximately Second, some would argue that the initial treatment in 70% in 1 year for a total of 53 patients with a diagnosis of a series of titrated seizures is a 'wasted' seizure, adding psychotic depression (61,62). These studies were retrospec­ to costs and potential cognitive side effects without any significant therapeutic benefit to the patient. The unilateral tive and could not examine compliance rates or the ade­ seizure at or near the seizure threshold used during the initial quacy of either the initial (pre-ECT) or continuation medi­ treatment setting to determine seizure threshold probably cation trial. However, the potential advantages of In a prospective study, Sackeim and co-workers (63) fol­ determining the seizure threshold and adjusting the subse­ lowed 58 patients for 1 year after ECT. They examined a quent seizures to the threshold has advantages in maximiz­ number of clinical variables including a retrospective review ing benefit and decreasing the potential for future ineffective of the adequacy of the pre-ECT medication trial. The most treatments (if the energy delivered is too low) and cognitive important factor in determining relapse on maintenance side effects (if the energy is too high). Patients (with and without ment for depression (55,58) and this data could obviate the psychotic features) who were rated as receiving a therapeutic need to determine seizure threshold. Because the majority medication trial(s) prior to their acute course of ECT re- of patients treated with ECT are older and older patients lapsed at a rate that was twice the rate found in patients have very high seizure thresholds, dose titrations at eight to who did not receive an adequate pre-ECT medication trial ten times threshold are generally at or above the 400-mC (64% versus 32%). The maintenance medication was not range used by McCall and associates. In fact, in some older standardized but the results indicated that the adequacy of 1102 Neuropsychopharmacology: The Fifth Generation of Progress the post-ECT medication trial was only marginally related senting for ECT after multiple failed medication trials and to the relapse rate and then primarily in patients who did there may be little benefit from yet another trial of an SSRI. The pa­ In fact the one medication regimen that has been shown tients who were not determined to be medication resistant to be effective in maintenance therapy is a combination of prior to ECT had a lower relapse rate when they received lithium and nortriptyline (discussed in the following). Sackeim and as­ benefit of this combination therapy may be owing to the sociates argue that many of these patients may have re­ fact that few patients had been given lithium augmentation sponded to antidepressant medication prior to ECT if they prior to their acute course of ECT. The overall relapse rate re­ Finally, maintenance ECT is similar to depot haloperidol mained very high (approximately 50%) and most of the in the treatment of schizophrenia and may provide prophy­ patients who relapsed did so in the first 4 months of this lactic benefit from improved compliance in patients who 1-year follow-up study. This finding indicates that the effi­ might otherwise not comply with their maintenance medi­ cacy of ECT may be relatively transient. Most studies of maintenance ECT only report pa­ ing medication resistance found in most ECT patient popu­ tients who complied with the treatment regimen. The expe­ lations, the clinical challenge is increasingly to determine rience at the Emory University Outpatient ECT program the most effective maintenance treatments and increasingly is similar to the data reported by Clarke and colleagues (67). There is ance with antidepressant medications; (c) can comply with clear evidence that these treatments are being used increas­ the overall treatment plan including behavioral restrictions ingly in clinical practice, yet there is a lack of guidelines to (i. The NIMH is presently funding three studies The guidelines for the use of C-ECT have been actively that will add significantly to our understanding of mainte­ discussed but there are little prospective data on which to nance ECT. Two multicenter trials are examining the effi­ base recommendations on frequency of treatments and how cacy of different maintenance strategies after an acute re­ long they should be continued or the nature of the potential sponse to ECT. Sackeim and colleagues are comparing cognitive side effects. A majority of the studies are case re- maintenance placebo, nortriptyline versus nortriptyline and ports and many predate antidepressant medication (66). Preliminary results More recent reports in patients with depression (66–74), from this line of investigation show that nortriptyline pro­ mania (75,76), and schizophrenia (77) describe a marked vides only marginally greater protection against relapse dur­ decrease in the number of hospitalizations, hospital days, ing the post-ECT period than does placebo, with relapse depressive symptoms, increased functional status, and stable rates of approximately 70% during the first year. The addi­ cognitive functioning for the period of continuation ECT. Charles Kellner is the principal investigator on a nance medication.

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