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By Q. Harek. Miami Christian University.

A placebo-controlled outpatient study of naltrex- but the data are limited (16 cheap tadacip 20 mg with mastercard,77) discount tadacip 20mg. The calcium channel antago- functional brain damage caused by cocaine including strokes nist nifedipine has been studied and shows some promise (16) cheap tadacip 20mg on-line. Structural imaging using computed tomographic scan- (68) tadacip 20 mg online. Nimodipine showed a reduction in the effects of intra- ning and magnetic resonance imaging (MRI) have shown venous cocaine as well as reductions in acute cocaine-related enlarged ventricles and sulci in cocaine abusers (79). Func- cardiovascular toxicity, but lamotrigine did not reduce co- tional neuroimaging studies have shown focal reductions in caine effects in a similar placebo-controlled crossover study regional cerebral blood flow(rCBF) among chronic cocaine (69,70). Memantine, a glutamate inhibitor, showed no effi- abusers (15–17). These defects also appear to be persistent cacy in reducing cocaine effects acutely (71). Outpatient for several weeks of abstinence at least, and can be associated placebo-controlled studies have not been done with these with neuropsychological deficits (15–17,80). Unfortu- normally high levels of phosphomonoesters and lowlevels nately, this agent is not available in the United States, and of nucleotide triphosphates compared to normals (81). However, baclofen, which is a involve vasoconstriction (82) and platelet abnormalities. Abnormal platelets may produce thrombosis No other controlled trials have been published with this or in cerebral vessels and produce blood flowalterations (18). One study in six cocaine-dependent nary test of 4 weeks of aspirin therapy led to a 50% improve- volunteers examined the effect of disulfiram 250 mg on ment in cerebral perfusion (16). In a placebo-controlled responses to intranasal cocaine (2 mg/kg) using a random- study that has just been completed, aspirin significantly re- ized double-blind, placebo-controlled design (75). Al- duced perfusion defects on single photon emission com- though disulfiram induced no significant differences in co- puted tomography (SPECT) imaging (84,85). It was a large, multisite psychother- apy clinical trial for outpatients who met the DSM-IV crite- Although the simplest peripheral blocking approach of pas- ria for cocaine dependence. For 480 randomized patients, sively injecting polyclonal antibodies to cocaine into a four treatments were compared over an 18-month period. One treat- ies would not last very long and might be of limited use as ment also added cognitive therapy, one added supportive- a sustained treatment. For any type of relapse prevention, expressive psychodynamic therapy, and one added individ- the immune response elements must remain at relatively ual drug counseling. The final group had drug counseling high levels for periods of several weeks or months, which alone. Two specific interaction hypotheses, one involving is best done by active immunization (86). However, three psychiatric severity and the other involving degree of antiso- other approaches using catalytic antibodies, monoclonal cial personality characteristics, were examined, but no major passive antibodies, or injections of butrylcholinesterase have findings related to these hypotheses have been found (88, some promise (87). Either of these was intensive, including 36 possible individual sessions and effects can cause a very significant reduction in the high or 24 group sessions for 6 months. All four of these approaches can also be monthly during active treatment and at 9 and 12 months combined and used together with the pharmacotherapies after baseline. Primary outcome measures were the Addic- described above. The only approach that has been tested tion Severity Index–Drug Use Composite score and the in humans is active immunization (86). The initial animal number of days of cocaine use in the past month. Compared studies showed excellent production of a highly specific an- with the two psychotherapies and with group drug counsel- tibody to cocaine. With active immunization the amount ing (GDC) alone, individual drug counseling plus GDC of inhibition of cocaine entering the brain ranged from 30% showed the greatest improvement on the Addiction Severity to 63% at 30 seconds after cocaine injection in rats. Individual group coun- amount of inhibition was sufficient to extinguish cocaine seling plus GDC was also superior to the two psychothera- self-administration in the rat model. In the initial human study of this vaccine, it was well Hypotheses regarding the superiority of psychotherapy to tolerated with virtually no side effects using a dose of 1,000 GDC for patients with greater psychiatric severity and the g given with two booster injections over a 3-month period superiority of cognitive therapy plus GDC compared with (88). The vaccine produced substantive quantities of anti- supportive-expressive therapy plus GDC for patients with body that was related to both the dose of vaccine and the antisocial personality traits or external coping style were not number of booster injections. Thus, compared with professional psychother- potential efficacy in relapse prevention for abstinent cocaine apy, a manual-guided combination of intensive individual abusers appear warranted. PSYCHOTHERAPIES Cognitive Behavioral Therapy (CBT) Professional Psychotherapy vs. Drug In spite of these overall discouraging results, cognitive be- Counseling havioral treatments have been among the most frequently Because of the limited efficacy of pharmacotherapy, the suc- evaluated psychosocial approaches for the treatment of sub- cess of behavioral and psychotherapies is important to con- stance use disorders and have a comparatively strong level sider. To date, more than 24 ran- use of professional therapies such as cognitive behavioral domized controlled trials have evaluated the effectiveness of therapy and supportive expressive therapies has been exam- cognitive behavioral relapse prevention treatment on sub- ined. Second, contingency management as a form of behav- stance use outcomes among adult tobacco smokers and alco- ioral therapy has gotten much attention and reasonable suc- hol, cocaine, marijuana, opiate, and other types of substance cess. These therapies have nowbeen extensively studied and abusers (93). Overall, these studies suggest that the average are increasingly being examined as treatments that might be effect size for CBT compared with control or comparison complemented by emerging pharmacotherapies. Review and many be more readily available to community pro- of this group of studies suggests that, across substances of grams. This body of literature also suggests that out- aimed at administering the drugs, even in the absence of comes in which CBT may hold particular promise include physical dependence (95). Thus, the A reviewof this series of studies can be found in Carroll goal of drug abuse treatment is to decrease behavior main- (93). CM procedures are one method of ment goal of abstinence and relapse prevention, CBT treat- accomplishing this goal, by presenting rewards or incentives ment has two critical components. A functional analysis is simply documented drug use (negative contingencies), or a combi- an exploration of cocaine use with respect to its antecedents nation of the two. The second critical component of CBT Higgins and colleagues (95–97) have demonstrated that is skills training. In CBT, a substantial portion of every CM procedures in combination with a community rein- session is devoted to the teaching and practice of coping forcement approach (CRA) facilitate initial abstinence in skills; in fact, CBT can be thought of as a highly individual- primarily cocaine-dependent persons. In the first, 12-week ized training program that helps cocaine abusers unlearn study (95), the CM procedure consisted of vouchers with old habits associated with cocaine abuse and learn or relearn a monetary value, which were presented upon evidence of more healthy skills and habits. The vouchers increased in value for every consecutively coping skills, changing reinforcement contingencies, foster- drug-free urine and were exchangeable for client-therapist ing management of painful affects, and improving interper- agreed-upon retail items and activities related to treatment sonal functioning. Treatment retention was significantly higher in the In a study comparing supportive therapy to CBT for behavioral treatment than standard drug counseling group. Cocaine outcomes were weeks 1 to 12 and lottery tickets in weeks 13 to 24 were comparable whether the patient received CBT or ClM, or presented contingent upon documented drug abstinence. Similarly, 68% and 42% of the clients in the behav- fewer urine screens positive for cocaine when treated with ioral treatment group achieved at least 8 and 16 weeks, CBT compared with ClM. CBT also was more effective respectively, of continuous cocaine abstinence as opposed than supportive ClM in retaining depressed subjects in to 11% and 5% in the standard drug abuse counseling treatment and in reducing cocaine use (94). In the third, 24-week study (97), cocaine-dependent been useful for medication development as a platform for individuals were randomized to receive either behavioral clinical trials because it meets the guidelines for an effective treatment without incentives or behavioral treatment with platform. Specifically, it is strong enough to hold patients incentives (i. The group that received the incentives showed signif- for any medication effects. As counterexamples, treatments icantly greater treatment retention (75% vs. Overall, rates of abstinence without any medications, but can serve the findings of these studies suggest that incentives contin- as excellent means to inducing initial abstinence. Contingency Management Procedures This voucher system also has been examined in a 12-week Contingency management (CM) procedures are based on clinical trial for its ability to facilitate cocaine abstinence in a behavioral perspective of drug abuse, which views drugs methadone-maintained cocaine abusers (98,99). The con- as powerful reinforcers maintaining high rates of behavior tingency group subjects achieved significantly longer dura- 1470 Neuropsychopharmacology: The Fifth Generation of Progress tions of sustained abstinence than yoked-controls (mean of motivation may be more cost-effective than increasing the 5. These vouchers may contribute to demoralization and a lack of findings suggest that vouchers also can be used as incentives perceived self-efficacy for succeeding in stopping drug use for drug abstinence in opioid-dependent cocaine abusers and thus contribute to a cycle of drug use and failure. One issue with CM dependence: (a) CM is of limited efficacy in this population. This issue CM is costly and not supported by current funding mecha- of continued efficacy after stopping medications has been nisms. Be- has yet to be fully explored, but recent reviews suggest it cause vouchers are used to support treatment goals, thera- may have a modest effect size of 0.

FIGURE 18-9 Am ino acid pools and am ino acid utilization in acute renal failure extraction of am ino acids observed in anim al experim ents order tadacip online from canada, (ARF) buy 20 mg tadacip with mastercard. As a consequence of these m etabolic alterations tadacip 20mg on-line, im bal- overall am ino acid clearance and clearance of m ost glucoplastic ances in am ino acid pools in plasm a and in the intracellular com - am ino acids is enhanced discount tadacip 20mg on line. In contrast, clearances of PH E, proline partm ent occur in ARF. A typical plasm a am ino acid pattern is (PRO ), and, rem arkably, VAL are decreased [16, 17]. Plasm a concentrations of cysteine (CYS), taurine (TAU), alanine; ARG— arginine; ASN — asparagine; ASP— aspartate; m ethionine (M ET), and phenylalanine (PH E) are elevated, where- CIT— citrulline; GLN — glutam ine; GLU— glutam ate; GLY— as plasm a levels of valine (VAL) and leucine (LEU) are decreased. As expected from the stim ulation of hepatic (From Drum l et al. Thus, loss of renal function can contribute to the altered am ino acid pools in ARF and to the fact that several am ino acids, such as arginine or tyrosine, which conventionally are term ed nonessential, m ight becom e conditionally indispensable in ARF (see Fig. In addition, the kidney is an im portant organ of protein degrada- tion. M ultiple peptides are filtered and catabolized at the tubular brush border, with the constituent am ino acids being reabsorbed and recycled into the m etabolic pool. In renal failure, catabolism of peptides such as peptide horm ones is retarded. This is also true for acute urem ia: insulin requirem ents decrease in diabetic patients who develop of ARF. W ith the increased use of dipeptides in artificial nutrition as a source of am ino acids (such as tyrosine and glutam ine) which are not soluble or stable in aqueous solutions, this m etabolic function of the kidney m ay also gain im portance for utilization of these novel nutritional substrates. In the case of glycyl-tyrosine, m etabol- ic clearance progressively decreases with falling creatinine clearance FIGURE 18-10 (open circles, 7 healthy subjects and a patient with unilateral M etabolic functions of the kidney and protein and am ino acid nephrectom y*) but extrarenal clearance in the absence of renal m etabolism in acute renal failure (ARF). Protein and am ino acid function (black circles) is sufficient for rapid utilization of the m etabolism in ARF are also affected by im pairm ent of the m eta- dipeptide and release of tyrosine. Infusion of arginine-free am ino acid solutions can cause life-threatening com - plications such as hyperam m onem ia, com a, and acidosis. H ealthy subjects readily form tyrosine from phenylalanine in the liver: During infusion of am ino acid solutions containing phenylalanine, plasm a tyrosine concentration rises (circles). In contrast, in patients with ARF (triangles) and chronic renal failure (CRF, squares) phenylalanine infusion does not increase plasm a tyrosine, indicating inadequate interconversion. Recently, it was suggested that glutam ine, an am ino acid that traditionally was designated non-essential exerts im portant m eta- bolic functions in regulating nitrogen m etabolism , supporting im m une functions, and preserving the gastrointestinal barrier. Thus, it can becom e conditionally indispensable in catabolic ill- ness. Because free glutam ine is not stable in aqueous solu- tions, dipeptides containing glutam ine are used as a glutam ine source in parenteral nutrition. The utilization of dipeptides in FIGURE 18-11 part depends on intact renal function, and renal failure can im pair Am ino acids in nutrition of acute renal failure (ARF): Conditionally hydrolysis (see Fig. N o system atic studies have been essential am ino acids. Because of the altered m etabolic environm ent published on the use of glutam ine in patients with ARF, and it of urem ic patients certain am ino acids designated as nonessential m ust be noted that glutam ine supplem entation increases nitrogen for healthy subjects m ay becom e conditionally indispensable to ARF intake considerably. Nutrition and M etabolism in Acute Renal Failure 18. The extent of protein catabolism can be assessed by calculating the urea nitro- gen appearance rate (UN A), because virtually all nitrogen arising Urea nitrogen appearance (UNA) (g/d) from am ino acids liberated during protein degradation is converted Urinary urea nitrogen (UUN) excretion to urea. Besides urea in urine (UUN ), nitrogen losses in other body fluids (eg, gastrointestinal, choledochal) m ust be added to any Change in urea nitrogen pool change in the urea pool. W ith known nitrogen (BW 2 BW1) BUN2/100 intake from the parenteral or enteral nutrition, nitrogen balance If there are substantial gastrointestinal losses, add urea nitrogen in secretions: can be estim ated from the UN A calculation. In the polyuric recovery phase in patients with sepsis-induced ARF, a nitrogen intake of 15 g/day (averaging an amino acid intake of 1. Several recent studies have tried to evaluate protein and am ino acid requirem ents of critically ill patients with ARF. Kierdorf and associates found that, in these hypercatabolic patients receiving continuous hem ofiltration therapy, the provision of am ino acids 1. Am ino acid and protein requirem ents of patients with acute renal Chim a and coworkers m easured a m ean PCR of 1. The optim al intake of protein or am ino acids is weight per day in 19 critically ill ARF patients and concluded that affected m ore by the nature of the underlying cause of ARF and protein needs in these patients range between 1. Sim ilarly, M arcias and coworkers have obtained a protein than by kidney dysfunction per se. Unfortunately, only a few stud- catabolic rate (PCR) of 1. In nonhypercatabolic patients, during the polyuric phase of ARF Sim ilar conclusions were drawn by Ikitzler in evaluating ARF protein intake of 0. The factors contributing to insulin resistance are m ore m ajor cause of elevated blood glucose concentrations is insulin or less identical to those involved in the stim ulation of protein resistance. Results from experim ental anim als sug- insulin-stim ulated glucose uptake by skeletal m uscle is decreased by gest a com m on defect in protein and glucose m etabolism : tyrosine 50 % , A, and m uscular glycogen synthesis is im paired, B. H owever, release from m uscle (as a m easure of protein catabolism ) is closely insulin concentrations that cause half-m axim al stim ulation of glu- correlated with the ratio of lactate release to glucose uptake. A second feature of glucose metabolism (and at the same time the dominating mechanism of accelerated pro- tein breakdown) in ARF is accelerated hepatic gluconeogenesis, main- ly from conversion of amino acids released during protein catabolism. Hepatic extraction of amino acids, their conversion to glucose, and urea production are all increased in ARF (see Fig. In healthy subjects, but also in patients with chronic renal failure, hepatic gluconeogenesis from amino acids is readily and completely suppressed by exogenous glucose infusion. In contrast, in ARF hepat- ic glucose formation can only be decreased, but not halted, by sub- strate supply. As can be seen from this experimental study, even dur- ing glucose infusion there is persistent gluconeogenesis from amino acids in acutely uremic dogs (•) as compared with controls dogs (o) whose livers switch from glucose release to glucose uptake. These findings have important implications for nutrition support for patients with ARF: 1) It is impossible to achieve positive nitrogen balance; 2) Protein catabolism cannot be suppressed by providing conventional nutritional substrates alone. Thus, for future advances alternative means must be found to effectively suppress protein catab- olism and preserve lean body mass. Profound alterations of lipid metabolism occur in patients with ARF. The triglyceride con- tent of plasma lipoproteins, especially very low-density (VLDL) and low-density ones (LDL) is increased, while total cholesterol and in particular high-density lipoprotein (HDL) cholesterol are decreased [33,34]. The major cause of lipid abnormalities in ARF is impair- ment of lipolysis. The activities of both lipolytic systems, peripheral lipoprotein lipase and hepatic triglyceride lipase are decreased in patients with ARF to less than 50% of normal. M aximal postheparin lipolytic activity (PHLA), hepatic triglyceride lipase (HTGL), and peripheral lipoprotein lipase (LPL) in 10 controls (open bars) and eight subjects with ARF (black bars). H owever, in contrast to this im pairm ent of lipolysis, oxidation of fatty acids is not affected by ARF. During infusion of labeled long-chain fatty acids, carbon dioxide production from lipid was com parable between healthy subjects and patients with ARF. Fat particles of artificial fat em ulsions for parenteral nutrition are degraded as endogenous very low-den- sity lipoprotein is. Thus, the nutritional consequence of the im paired lipolysis in ARF is delayed elim ination of intravenously infused lipid em ulsions [33, 34]. The increase in plasm a triglyc- erides during infusion of a lipid em ulsion is doubled in patients with ARF (N =7) as com pared with healthy subjects (N =6). The clearance of fat em ulsions is reduced by m ore than 50% in ARF. The im pairm ent of lipolysis in ARF cannot be bypassed by using m edium -chain triglycerides (M CT); the elim ination of fat em ul- sions containing long chain triglycerides (LCT) or M CT is equally retarded in ARF. N evertheless, the oxydation of free fatty acid released from triglycerides is not inpaired in patients with ARF. ARF frequently is associated with hyper- kalem ia and hyperphosphatem ia. Causes are not only im paired renal excretion of electrolytes but release during catabolism , altered Hyperkalemia Hyperphosphatemia distribution in intracellular and extracellular spaces, im paired cellular uptake, and acidosis. Thus, the type of underlying disease Decreased renal elimination Decreased renal elimination and degree of hypercatabolism also determ ine the occurrence and Increased release during catabolism Increased release from bone severity of electrolyte abnorm alities. Decreased cellular uptake/ Decreased cellular uptake/utilization increased release and/or increased release from cells Metabolic acidosis: 0.

Different types of opiates and modes of administration have different speeds of onset and effects best purchase for tadacip. The modes of administration include swallowing buy tadacip with american express, snorting purchase tadacip 20mg with visa, smoking tadacip 20mg overnight delivery, and subcutaneous and intravenous injection. The classic heroin withdrawal syndrome appears in 4-12 hours, peaks at 48-72 hours, and subsides by 7-10 days. Objective measures include tachycardia, hypertension, lacrimination, rhinorrhoea, dilated pupils, and “goose flesh” (piloerection; “going cold turkey”). There is evidence that the expectations of the withdrawing individual greatly experience Pridmore S. Those who are most fearful and expect to suffer are those who most suffer. Dalrymple (2006) states the “pain” of withdrawal has been greatly exaggerated by poets and other “romantic writers”, and that this distortion has entered lay and professional belief systems. Physical harm depends on the route of administration and adulterants. The risk of viral transmission (HIV, hepatitis B and C) led to the “harm minimization” focus of services (“needle exchange” being a feature). Psychiatric comorbidity has been demonstrated in 70% of heroin users, predominantly antisocial personality disorder (Seiveright & Daly, 1997), alcohol dependency, and depressive symptoms. However, it is more lipophilic than morphine and provides a stronger “rush”. Methadone is an orally effective opiate with a longer half-life than heroin (24-36 hours), which makes it suitable for daily administration. At above 80 mg per day it provides a reasonable level of opiate receptor blockade, such that euphoria from illicit drugs “used on top” is disinhibited. It has been the mainstay of treatment of opiate dependency in the western world. Buprenorphine is a partial mu receptor agonist and kappa receptor antagonist, which is being used in the stabilization and detoxification of opiate using people. Management of opiate dependency begins with a trusting patient-doctor relationship. Methadone may be used as a substitute for the previously used opiates. It is prescribed long-term with the aim of achieving stable (non-injecting) opiate dependence (methadone maintenance). The benefits include reduced risks from injecting, other drug use, criminal behaviour, and suicide/overdose, and increased likelihood of maintenance of treatment contact. Methadone should be part of a multidisciplinary, biopsychosocial treatment package (Gossop et al, 2006). Relapse prevention elements include identification of cues or triggers for craving (people, places, paraphenalia, moods) and techniques to handle high-risk situations (distraction, relaxation, imagery). Motivational interviewing aims to move people along in the “cycle of change”, from pre-contemplatiory (no interest in changing behaviour) to contemplation, and then to determination and action. Interestingly, before he developed the field of psychoanalysis, Sigmund Freud pioneered the use of cocaine as an analgesic in eye surgery. The stimulants increase energy and elevate mood, due to enhanced dopamine and noradrenaline activity. A more potent street preparation of methylamphetamine is “ice”, and a more potent form of cocaine is “crack”. The stimulants can be swallowed, snorted, or injected. As with other illegal substances, stimulant use is more common among young males of lower socio-economic status, in areas with high rates of other social problems. In Australia about 2% of the population has used cocaine. These are mainly inner-city polysubstance users (Hando et al, 1997). Methylamphetamine use is associated with increased violence, independent of psychosis (McKetin et al, 2014). The psychosis may be managed by cessation of the stimulant and commencement of an antipsychotic medication (often in an inpatient setting). There is some debated about whether the stimulants are “addictive”. The con argument is that the listed “withdrawal” symptoms are not true withdrawal, but simply “catching up” eating and sleeping. This semantic argument is a legacy of Cartesian dualism, and psychological dependency is frequently observed. Chronic exposure of rodents to stimulants causes increased dendritic branching and increased numbers of dendritic spines. The number closest to the neuron is a measure of dendritic branching, the number to the right is a measure of the number of dendritic spines. For both amphetamine and cocaine, the dendritic branching and spines numbers are up by 8-12%. Complications are more common with injecting, and when there is concurrent use of other drugs. There is little evidence to support any specific treatment of stimulant use, however, recently, bupropion was described as useful in methamphetamine abuse/dependence (Heinzerling et al, 2013). There is the promise of a unique approach: a cocaine vaccine which will slow entry of the substance into the brain (Sofuoglu & Kosten, 2006). It is popular and has been taken by 13% of 3000 UK university students (Webb, et al, 1996), and 4. Ecstasy causes the release of serotonin from nerve terminals. It also inhibits tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, resulting in central serotonin depletion. Lowering of mood is frequently reported in the post use period, which is consistent with depletion of central serotonin. Ecstasy has both stimulant and hallucinogenic effects. It also causes an altered state of consciousness and profound feelings of attachment and connection. Physical effects are reminiscent of amphetamines use, with tachycardia, anorexia, increased motor activity, bruxism (teeth grinding), elevated temperature, and sweating. Animal evidence indicates MDMA is toxic to serotonergic neurons. Human neurotoxicity has not been conclusively demonstrated, but the evidence is strong (Gouzoulis-Mayfrank & Daumann, 2006). As mentioned above, Kish et al (2010) have shown reduced serotonin transporter density throughout the cortex of MDMA users compared to healthy controls. These losses are greatest in the insula and occipital cortex. Mental complication include anxiety and panic, major depression, prolonged depersonalization, suicidal ideation, and psychosis. Physical complications are more common when taken in combination with other substances and include hyperthermia, dehydration, idiosyncratic organ failure of heart and liver, and cerebral oedema. The serotonin and neuroleptic malignant syndromes have been described. The principal psychoactive component: delta-9-tetrahydrocannabinol (THC). Cannabis may be eaten, but the most efficient and common mode is smoking. A specific receptor (for the endogenous ligand anandamide) is located in regions associated with memory, reward, pain perception and motor co-ordination. A New Zealand study (Boden et al, 2006) found that by 25 years of age, 76. Acute mental effects include euphoria and relaxation, perceptual alterations (time distortion), intensification of ordinary sensory experiences (for example, while eating and listening to music) and impaired short-term memory and attention. Impairment in cognition and behavioural functions, such as driving are dose-related. The most commonly reported adverse mental effects are anxiety and panic reactions, and these may lead to discontinuation by naïve users.

Early reports with this test indicated a high sensi- tivity and specificity (95% to 100% ) in identifying RVH T if all FIGURE 3-18 three of the renin criteria listed here were m et discount 20mg tadacip amex. Subsequent The captopril test: renin criteria that distinguish patients with reports have not been as encouraging such that the overall sensi- renovascular hypertension from those with essential hypertension 20 mg tadacip. A buy cheap tadacip 20mg online, TcDPTA tim e-activity curves during asym m etry of renal size and function and on specific discount tadacip 20mg free shipping, captopril- baseline. B, TcDPTA tim e-activity curves after captopril adm inis- induced changes in the renogram, including delayed time to maximal tration. These curves represent a captopril renogram in a patient activity (≥11 m inutes), significant asym m etry of the peak of each with unilateral left renal artery stenosis. This diagnostic test has been kidney, m arked cortical retention of the radionuclide, and m arked used to screen for renal artery stenosis and to predict renovascular reduction in the calculated glom erular filtration rate of the kidney hypertension. Captopril renography appears to be highly sensitive ipsilateral to the stenosis. O ne m ust interpret the clinical and reno- and specific for detecting physiologically significant renal artery graphic data with caution, as protocols are com plex and diagnostic stenosis. Scintigrams and time-activity curves should both be analyzed criteria are not well standardized. N evertheless, captopril renogra- to assess renal perfusion, function, and size. If the renogram following phy appears to be an im provem ent over the captopril provocation captopril administration is abnormal (panel B, demonstrating delayed test, with m any reports indicating sensitivity and specificity from time to maximal activity and retention of the radionuclide in the right 80% to 95% in predicting an im provem ent in blood pressure kidney), another renogram may be obtained without captopril for following intervention. The diagnosis of renal artery stenosis is based on with perm ission. A brief duration of moderately severe hypertension is the m ost im portant clue Low (<1%) PRA M oderate (≈5%–15%) High (>25%) directing subsequent work-up for RVHT. Alternatively, in patients highly suspected to have RVHT, a captopril Captopril test, or captopril renogram, or stimulated renal vein renins, renogram followed by a renal arteriogram or (? Strong argum ents against RVHT include 1) long duration (more than 5 years) of hypertension, 2) old age, No further work-up Negative Positive Arteriogram + renal 3) generalized atherosclerosis, 4) increased vein renins serum creatinine, and 5) a normal serum potassium concentration. For these patients, particularly if the blood pressure is only mini- FIGURE 3-20 mally elevated or easily controlled with one or Suggested work-up for renovascular hypertension. Because the prevalence of renovascular hyper- two antihypertensive medications, further tension (RVHT) among hypertensive persons in general is approximately 2% or less, widespread work-up for RVHT is not indicated. Despite the proliferation of diagnostic tests from M ann and Pickering; with permission. This patient presented in 1977 with a recent appearance of hypertension and a blood pressure of 170/115 m m H g. Three years previously, when diagnosed with polycythem ia vera, an IVP was norm al. She was fol- lowed closely between 1974 and 1977 by her physician and was always norm otensive until the hypertension suddenly appeared. A repeat rapid sequence IVP dem onstrated a reduction in the size of the left kidney from 14 cm in height (1974) to 11. The renal arteriogram shown here indi- cates high-grade bilateral renal artery stenosis with the left kidney m easuring 11. Renal vein renins were obtained and lateralized strongly to the sm aller left kidney. The blood pressure was well controlled with inderal and chlorthalidone. Right aortorenal reim plantation was undertaken solely to preserve renal function. Blood pressure continued to require antihypertensive m edication, but was controlled to norm al levels with inderal and chlorthalidone. Renovascular Hypertension and Ischemic Nephropathy 3. This figure describes eight patients hospitalized because of severe hypertension and renal insufficiency. W ith m ed- ical m anagem ent of the hypertension (antihypertensive drug thera- py), four of the eight patients developed substantial worsening of B their renal function as m easured by serum creatinine; three of these four patients dem onstrated im provem ent following surgery or FIGURE 3-23 angioplasty. The other four patients (patients one to four) did not Im proved renal function dem onstrated by intravenous pyelography dem onstrate a worsening serum creatinine level with m edical thera- following left renal revascularization. A, preoperative IVP (5-m inute py; but three of these four patients showed im proved renal func- film ) in a 65-year-old white m an with a 15-year history of hyperten- tion following surgery or angioplasty. Note poorly functioning left kidney, coworkers; with perm ission. B, post operative IVP (5-m inute film) obtained following left aortorenal saphenous vein bypass grafting to the left kidney. N ote the prom pt function and increased height (14. Two definitions of ischem ic nephropathy are suggested herein: 1) clinically significant reduction in renal function due to compromise of the renal circulation; and 2) clinically significant reduction in glom erular filtration rate due to hem ody- namically significant obstruction to renal blood flow, or renal failure due to renal artery occlusive disease. Atherosclerotic renal artery stenosis is common in older patients with and without hypertension simply as a Patients, n Percent of patients with >50% stenosis consequence of generalized atherosclerosis Abdominal aortic aneurysm 109 38 obliterans. Approximately 40% of consecu- Aorto-occlusive disease 21 33 tively studied patients undergoing arteriography Lower extremity disease 189 39* for routine evaluation of abdominal aortic Suspected renal artery stenosis 76 70† aneurysm, aorto-occlusive disease, or lower Coronary artery disease 76 29† extremity occlusive disease have associated 817 20‡ renal artery stenosis (more than 50% unilateral renal artery stenosis) and nearly 30% of *50% in diabetic patients. Correlations of hyper- cholesterolem ia and cigarette sm oking with renal artery atherosclerosis are not unequiv- ocally clear, but they probably represent risk factors for renal artery atherosclerosis just as they represent risk factors for atherosclerosis in other vascular beds. The clinical presen- ISCHEM IC RENAL DISEASE tation of a patient likely to develop renal failure from atheroscle- rotic ischem ic renal disease is that of an older (m ore than 50 years) individual dem onstrating progressive azotem ia in conjunction with Acute renal failure, frequently precipitated by a reduction in blood pressure antihypertensive drug therapy, risk factors for generalized athero- (ie, angiotensin-converting enzyme inhibitors plus diuretics) sclerosis obliterans, known renal artery disease, refractory hyper- Progressive azotemia in a hypertensive patient with known renal artery stenosis tension, and generalized atherosclerosis. Acute renal failure precipi- treated medically tated by a reduction in blood pressure below a “critical perfusion Progressive azotemia in a patient (usually elderly) with refractory hypertension pressure,” and particularly with the use of angiotensin converting- Unexplained progressive azotemia in an elderly patient enzym e inhibitors (ACEI) or angiotensin II receptor blockers plus Hypertension and azotemia in a renal transplant patient diuretics, strongly suggests severe intrarenal ischem ia from arterio- lar nephrosclerosis and/or severe m ain renal artery stenosis. Unexplained progressive azotemia in an elderly patient with clinical signs of vascular disease with minimal proteinuria and a bland urinary sedim ent also suggest ischem ic nephropathy. Underlying the concept of renal revascularization for preservation of renal function is the notion that athero- sclerotic renal artery disease (ASO -RAD) is a progressive disorder. The sequential angiogram s in Figures 3-26 and 3-27 show angiographic progression of ASO -RAD over tim e. In patients dem onstrating progressive renal artery stenosis by serial angiography, a decrease in kidney function as m easured by serum creatinine and a decrease in ipsilateral kidney size correlate significantly with pro- gressive occlusive disease. Patients dem on- strating m ore than 75% stenosis of a renal artery are at highest risk for progression to com plete occlusion. RENOVASCULAR DISEASE Clinical clues to the high-risk patient are sim ilar to the clinical presentations of ischemic renal disease shown in Figure 3-25. Nearly 75% of adults with a unilateral sm all kidney have sustained this renal atrophy due to large vessel occlusive disease from atherosclerosis. Generalized atherosclerosis obliterans O ne third of these patients with a unilateral sm all kidney have Presumed renovascular hypertension high-grade stenosis of the artery involving the contralateral normal- Unilateral small kidney sized kidney. Flash pulm onary edem a is another clue to bilateral Unexplained azotemia renovascular disease or high-grade stenosis involving a solitary Deterioration in renal function with BP reduction and/or ACE inhibitor therapy functioning kidney. These patients, usually hypertensive and with Flash pulmonary edema docum ented coronary artery disease and underlying hypertensive heart disease, present with the abrupt onset of pulm onary edem a. Left ventricular ejection fractions in these patients are not seriously im paired. Flash pulm onary edem a is associated with atherosclerotic FIGURE 3-28 renal artery disease and may occur with or without severe hypertension. Clinical clues to bilateral atherosclerotic renovascular disease. Renal revascularization to preserve kidney function or to prevent The patient at highest risk for developing renal insufficiency from life-threatening flash pulmonary edema may be considered in patients renal artery stenosis (ischem ic nephropathy) has sufficient arterial with high-grade arterial stenosis to a solitary kidney or high-grade stenosis to threaten the entire renal functioning m ass. Pecutaneous translum inal renal risk patients have high-grade (m ore than 75% ) arterial stenosis angioplasty (PTRA), renal artery stenting, or surgical renal revascu- to a solitary functioning kidney or high-grade (m ore than 75% ) larization m ay be em ployed. Patients with chronic total renal artery bilateral renal artery stenosis. Patients with two functioning occlusion bilaterally or in a solitary functioning kidney are candidates kidneys with only unilateral renal artery stenosis are not at for surgical renal revascularization, but are not candidates (from a significant risk for developing renal insufficiency because the technical standpoint) for PTRA or renal artery stents. Clinical clues suggesting PREDICTORS OF KIDNEY SALVAGEABILITY renal viability include 1) kidney size greater than 9 cm (pole-to- pole length) by lam inography (tom ography); 2) som e function of the kidney on either urogram or renal flow scan; 3) filling of distal renal arteries (by collaterals) angiographically, when the Kidney size >9 cm (laminography) m ain renal artery is totally occluded proxim ally (see Fig.

Australian and New Zealand Journal of Psychiatry 2013; 47: 884 buy discount tadacip 20mg. Suicidality in chronic pain: a review of the prevalence tadacip 20 mg mastercard, risk factors and psychological links tadacip 20mg overnight delivery. Assessing the short term health impact of the Great Recession in the European Union cheap tadacip 20mg mastercard. American Journal of Psychiatyry 2010; 167:1425-1427. Genetics of suicide: a systematic review of twin studies Wiener Klinische Wochenschrift 2007; 119:463-475. Probably not… Alliance for Hope for Suicide Survivors. Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Understanding deliberate self harm: an enquiry into attempted suicide. Zouk H, Tousignant M, Seguim M, Lesage A, Turecki G. Characterization of impulsivity in suicide completers: clinical, behavioral and psychosocial dimensions. Journal of Affective Disorders 2006; Mar 15 [Epub ahead of print]. This cartoon compares old and new psychiatric facilities. It (this cartoon) is a statement that currently, most aspects of life are medicalized, and as a result, people are being admitted (at their request) to psychiatric wards, who have problems with living rather than psychiatric disorders. In this chapter the focus is on medicalization in the field of psychiatry. The term “psychiatricization” (Knezevic & Jovancevic, 2001) has been used in the title to emphasise the point. However, as the term medicalization is more widely understood and used in the scientific literature, it will be used in the text. For present purposes all we can say is that distress, like pain, is an unwanted state. Contact with unpleasant things is painful; not getting what one wishes is painful” (The Sermon at Benares). Psychiatry is now dealing with distress which (in the opinion of some) is not the responsibility of psychiatry. For example, psychiatry is now expected to assist (up to and including hospitalisation) when individuals have social difficulties and are distressed following relationship breakdowns. Western society is now wanting psychiatry to deal with forms of distress for which we once relied on friends and extended family (Jacob, 2006); help for which the profession lacks a theoretical framework and practical capacity. Many factors favour this “dumping” of individuals on Psychiatry. But this does not mean psychiatry has an automatic, primary role in the management of situational crises. The problem of definitions We have problems because of the lack of clear definitions. In 1946, with the best intentions, the World Health Organization made matters much worse. The first line of the Constitution of the WHO gives the definition of heath as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”. Space does not permit a full analysis of this definition, but the words “complete physical, mental and social well-being” indicate the need for economic, social, political and judicial influences which are way beyond those of health professionals. Psychiatry is relatively defenceless against the “dumping” of social problems on the doorstep, again because of the lack of clear definition of its “territory”. Neither of the diagnostic systems (DSM-5, ICD-10) satisfactorily define mental disorder. Psychiatrists are often forced to admit distressed people with social problem because if they refuse admission and a suicide occurs (a danger which attends all distress), the coroner and newspapers will be condemnatory. In her book, The Broken Brain, Nancy Andreasen (1984) observed that the question, “What is mental illness? This may have been so in 1984, but it is not so in 2013. Most would agree that schizophrenia, bipolar disorder and obsessive-compulsive disorder are all mental disorders/illnesses; but what of “sexual addiction”, “antisocial/sociopathic personality disorder”, “burn out” and excessive shyness? Medicalization/psychiatricization of daily life Medicalization is the defining of non-medical problems in medical terms, usually as an illness or disorder, and usually with the implication that a medical intervention or treatment is appropriate (Zola, 1972). Medicalization leads to “normal” human behaviour and experience being “re-badged” as medical conditions (van Praag, 2000). An early claim of medicalization (too sweeping, in the opinion of many) was the book, The Manufacture of Madness, by Thomas Szasz (1970). Double, (2002) more recently stated, “Mental health care may function as a panacea for many different personal and social problems”. It is claimed both birth (Shaw, 2012) and death (Goh, 2012) have been medicalized. Initially, the medical profession was held solely responsible for the phenomenon of medicalization, and the term “medical imperialism” was coined. For example, on the rebadging “deviance” as a series of medical disorders, sociologist Ian Robertson (1987) writes, “They have become so only because physicians – and particularly psychiatrists – have successfully claimed authority over them”. While this has been and continues to be part of the explanation, the complete answer includes broader community factors (Scott, 1990). The current “engines driving medicalization” have been identified as biotechnology (especially the pharmaceutical industry and genetics), consumers, and managed care (Conrad, 2005; Iriart et al, 2011). Dr Juan Garcia of New Zealand (personal communication) has pointed out that in literature (which is a fair proxy for the real world) medicalization may have nothing to do with doctors, and in fact, doctors may dispute the presence of any disorder. He points to two example in Macbeth by William Shakespeare (circa, 1607). The first is when Macbeth sees a ghost and his guests respond, “Gentlemen, rise, his highness is not well. The second occurs when Lady Macbeth walks and talks in her sleep. A physician is called who states “More needs she the divine than the physician”. The majority of psychiatrists working in public general hospitals lament the emergence of medicalization/psychiatricization, which has allowed the community (citizens, police, courts, and welfare agencies) to force clinical psychiatrists to accept responsibility for situations/problems over which they have no real influence. A good case can be made for the validity of psychiatric disorders such as schizophrenia, major depressive disorder, bipolar disorder and obsessive compulsive disorder. And, using “evidence based” protocols, the psychiatrist is capable of providing the best possible management for people suffering these disorders. Disorders of interest Critics raise doubts about the validity of some recently described “disorders”, many spawned by the medicalization of the difficulties of everyday life (distress). The following table lists some behaviours and potentially matching diagnoses. The intention is not to discredit these diagnostic categories, but to illustrate the potential for normal behaviour to be cast as a mental disorder. Behaviour Diagnosis Shyness Social anxiety disorder Naughtiness Conduct disorder, Childhood onset Conduct disorder, Adolescent onset Delayed language Expressive language disorder Active Hyperactivity disorder Promiscuity Sexual addiction (Schaeffer, 1997) Sexually disinterested Hypoactive sexual desire disorder Unsatisfactory erections Male erectile disorder Unsuccessful gambling Pathological gambling Amorality Antisocial personality disorder Violence Intermittent explosive disorder Apprehension Agoraphobia (specific places) Specific phobia (except places) Social phobia (social anxiety disorder) Worried Generalized Anxiety Disorder Stress at work Work stress (Wainwright & Calnan, 2002) Stress Acute stress disorder Dependent Dependent personality disorder Narcissistic Narcissistic personality disorder Attention seeking Histrionic personality disorder Factitious disorder Avoidant Avoidant personality disorder Isolative Schizoid personality disorder Excessive coffee use Caffeine intoxication Caffeine induced sleep disorder Caffeine induced anxiety disorder Smoking Nicotine dependence Excessive alcohol use Alcohol intoxication Alcohol abuse Excessive cannabis use Cannabis intoxication Cannabis abuse Pridmore S. Distress is frequently misclassified as Major depressive disorder or PTSD. Nevertheless, it is frequently medicalized by rd commentators, thus becoming a 3 topic of interest. Depression (Major depressive disorder) See Chapter 8 for additional details. Clinicians who work in psychiatric wards do not doubt the existence of Major depressive disorder. Episodes last months, but may be shortened by treatment. Early episodes may be triggered by undesired events (loss). Later episodes may occur spontaneously, without detected triggering events. Depressed (sad, unhappy) mood is one, but only one, of the symptoms of Major depressive disorder (and related psychiatrically recognised conditions such as bipolar disorder), but depressed mood alone, is not sufficient to justify the diagnosis.

Self-care support is challenging when patients have more than one LTC order tadacip now. Whole-systems development is needed to facilitate the integrated delivery of self-care support services buy 20mg tadacip amex. Further research is required to identify which models of self-care support (if any) are effective for children and young people with multiple LTCs discount 20mg tadacip with mastercard. Self-care can be expensive and can impact differently on different families buy tadacip 20mg otc. The costs of self-care support to children, parents and families should be quantified. We thank Dr Katherine Stothard, Dr Gill Norman and Professor Karina Lovell for their help with abstract screening and study eligibility judgements and Irene Sanchez for her help with the quality appraisal of economic evaluations. We are grateful to Caitlin McWilliams for her help in preparing the report. We especially thank the children and young people, parents and health professionals who gave up their time to join our PPI advisory panel and whose experiences, thoughts and recommendations have shaped and informed our review. Contributions of authors Penny Bee wrote the protocol for the study, managed the project, assessed studies for inclusion, extracted data on all studies, facilitated PPI contributions and had primary responsibility for writing the report. Rebecca Pedley assessed studies for inclusion, extracted data on all studies, conducted analyses and wrote the report. Amber Rithalia assessed studies for inclusion, extracted data on all studies and assisted with analyses. Gerry Richardson contributed to the protocol for the study, extracted data on economic evaluations, advised on economic methodology and contributed to the writing of the report. Steven Pryjmachuk contributed to the protocol for the study, assessed studies for inclusion and contributed to the writing of the report. Susan Kirk contributed to the protocol for the study, assessed studies for inclusion, facilitated PPI contributions and contributed to the writing of the report. Peter Bower contributed to the study protocol, guided review procedures, extracted study outcome data, led data analysis and contributed to the writing of the report. Data sharing statement This is a secondary research study and, therefore, no primary data have been generated. Further information can be obtained from the corresponding author. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 49 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. 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Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Griffiths C, Foster G, Ramsay J, Eldridge S, Taylor S. How effective are expert patient (lay led) education programmes for chronic disease? Guendelman S, Meade K, Benson M, Chen YQ, Samuels S. Improving asthma outcomes and self-management behaviors of inner-city children: a randomized trial of the Health Buddy interactive device and an asthma diary. Stevens CA, Wesseldine LJ, Couriel JM, Dyer AJ, Osman LM, Silverman M. Parental education and guided self-management of asthma and wheezing in the pre-school child: a randomised controlled trial. McPherson AC, Glazebrook C, Forster D, James C, Smyth A. A randomized, controlled trial of an interactive educational computer package for children with asthma. 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