By B. Ugo. Cornerstone University.

Rate here the degree of unusualness order motrin 400mg online midwest pain treatment center wausau, not the degree or disorganisation of thought processes purchase motrin 600mg mastercard st john pain treatment center. BLUNTED AFFECT Reduced emotional tone, apparent lack of normal feeling or involvement. EXCITEMENT Heightened emotional tone, agitation, increased reactivity. DISORIENTATION Confusion or lack of proper association for person, place or time. Last modified: November, 2017 1 CHAPTER 8 SADNESS AND DEPRESSION [Please note: Two depression scales are available, after the references. Readers may choose to print the text only, without these additional pages. By this is meant, certain aspects of “normal” human behaviour and experience get “re-badged” as medical conditions. An example: what was formerly described as promiscuous or self indulgent sexual behaviour is being “diagnosed” in pop-psychology as “sexual addiction”. Chapter 32 deals in detail with “medicalization” in detail. It is profoundly important that we understand that sadness (low/depressed mood) is a part of the human experience – when people are sad for good reason we should give them support, but we must not call them “sick” until they have sufficient symptoms to justify the diagnosis. Some very clever people make the point that we must not consider every person who is experiencing an unpleasant emotions to be a “patient”. Sociologists Horwitz & Wakefield (2007) wrote the important book, “The Loss of Sadness: How psychiatry transformed normal sorrow into depressive disorder”. More recently, distinguished psychiatrist Allen Frances (2013) wrote the book “Saving Normal” – in which he demonstrates that many normal reactions are being called illness/sickness.

Evidence to support this obtaining a full history and performing a mental and physi- notion comes from postmortem neurochemical studies cal examination are essential steps toward making a firm comparing dopaminergic activities in DLB with those in clinical diagnosis purchase 400 mg motrin visa gallbladder pain treatment diet. As with suspected cases of AD cheap motrin 400 mg amex pain treatment quotes, the level PD and AD (59). In these studies, dopamine D2 receptor and extent of laboratory investigations vary according to binding was reduced in the caudal putamen and was signifi- the clinical picture, associated comorbidity, and physical cantly lower than in PD at all levels. However, because of the particular Although the increased falls reported in DLB may be associations of DLB with fluctuations in attention and cog- multifactorial, it is likely that more widespread involvement nition and visual hallucinations, both very commonly asso- of brainstem nondopaminergic nuclei is a contributing fac- ciated with a variety of other organic disorders, the investi- tor. Degeneration of the predominantly cholinergic pedun- gation of a suspected case of DLB requires a very careful culopontine nucleus is a likely explanation because neuronal laboratory evaluation. This usually includes routine hema- loss in this structure has been associated with postural insta- tology and biochemistry, determinations of erythrocyte bility (78). In addition, degeneration of the pedunculopon- sedimentation rate and creatine phosphate, thyroid function tine nucleus has been implicated as the pathophysiologic tests, measurements of B12 and folate levels, syphilis serol- basis for REM sleep behavioral disorder, which is also re- ogy, and urinalysis. A chest roentgenogram may also be ported in DLB (79). As in the diag- nosis of AD, neuroimaging investigations are often helpful, Neurochemical both in excluding other intracranial disorders (including As yet, only a few clinical–neurochemical relationships have cerebrovascular disease) that may be responsible for the cog- been identified in DLB. In earlier reports of the loss of nitive impairment and in providing supportive features for cholinergic activity from the cortex, correlations were iden- the diagnosis. DLB patients; loss of alpha rhythm and transient slow-wave In regard to noncognitive or neuropsychiatric symptoms, activity in the temporal lobe areas are the most common patients with visual hallucinations have significantly lower changes (82). Patients with AD are less likely to have tran- levels of choline acetyltransferase than do nonhallucinators sient slow waves, and slowing of the dominant rhythm is (80); recently, they have also been found to have lower less marked. However, the positive predictive value of the levels of nicotinic -bungarotoxin receptor binding in visual EEG in suspected cases of DLB has not been assessed in a association cortex (Ballard et al. Increasingly, some M1 binding in temporal cortex is increased in patients expe- form of structural imaging is becoming essential to apply riencing persistent delusions (81). Delusional misidentifica- diagnostic criteria rigorously, such as the NINCDS/ tion has also been associated with lower levels of -bungaro- ADRDA criteria for AD, the NINCS/ADRDA criteria for toxin binding in this region (Ballard et al. Disturbances in consciousness are associated with a ten- dency for choline acetyltransferase to be lower in the tha- Structural Imaging Changes lamic reticular nucleus (53) and with a relative preservation of the high-affinity nicotinic receptor in the cortex (Ballard Few studies have investigated computed tomographic (CT) et al.

MONOAMINERGIC SYSTEMS The involvement of the dopaminergic system is the other DOPAMINERGIC consistent neurochemical feature of DLB (Table 91 generic motrin 400mg amex pain treatment center of franklin tennessee. Earlier reports that dopamine loss Receptors was in some cases severe despite the absence of neurologic D1 receptorc c symptoms (49) motrin 400 mg generic pain management treatment for fibromyalgia, a finding that was interpreted to indicate D2 receptor /↓ c compensatory striatal pathology, need to be replicated in D3 receptor →/ SEROTONINERGIC prospectively assessed cases because symptoms may have Presynaptic been overlooked in psychogeriatric clinics; furthermore, Serotonin neuroleptic medication reduces striatal dopamine. Although Striatum in PD striatal dopamine deficits are more marked in caudal Cortex Serotonin transporter regions, particularly putamen, in DLB the loss of dopamine Cortex transporter is similar at different rostral caudal levels (59). Receptors Whereas in PD dopamine D2 receptors are up-regulated, 5-HT2A receptor at least in earlier stages of the disease, receptors are not Cortex →/ NORADRENERGIC increased in DLB and in particular are not up-regulated as a Noradrenaline result of neuroleptic medication (60). In addition to striatal Striatum dopamine deficits, dopamine losses in cortical areas also Cortex ↓ occur (Table 91. MAO-B ↑ The significance of the serotoninergic, noradrenergic, 5-HT, 5-hydroxytryptamine; AChE, acetylcholinesterase; and neuropeptide (e. The clinical significance of some of the cho- aSummary of neurochemical findings, reviewed Perry et al. Chapter 91: Dementia with Lewy Bodies 1307 GENETICS AD at a similar stage of dementia. The polymorphism caus- ing the K allele in the gene for butyrylcholinesterase has Familial cases of DLB have been reported, although the been reported to be associated with AD, although this find- majority of cases appear to be sporadic. Following the dis- ing has not been replicated by others. In DLB, an increased covery of two separate missense mutations in the -sy- number of butyrylcholinesterase K homozygotes have been nuclein gene on chromosome 4 in a small number of fami- found. It has been suggested that this genotype may partly lies with pathologically confirmed early-onset PD, mutation explain the enhanced responsiveness to cholinesterase inhib- screening was undertaken in this gene in both familial and itors in DLB (73). Although abnormalities in butyrylcho- sporadic cases of DLB (61). These studies failed to reveal linesterase are evident in AD, including elevated enzymatic any nucleotide changes within the exons screened. Such an influence may be via so-called susceptibility genes.

The initial glom erular vasoconstriction that follows the injection of radiocontrast m edium induces the ↑Endothelin Systemic ↓ATPase liberation of both vasoconstrictor (endothelin purchase motrin 600 mg with mastercard pain treatment center of southwest georgia, vasopressin) and ↑PGE2 ↑Vasopressin hypoxemia ↑ANF ↑Adenosine Osmotic load vasodilator (prostaglandin E2 [PGE2] motrin 600mg fast delivery midwest pain treatment center ohio, adenosine, atrionatiuretic ↑Blood viscosity to distal tubule ↓PGI factor ) substances. The net effect is reduced oxygen deliv- 2 ery to tubule cells, especially those in the thick ascending lim b of H enle. Because of the system ic hypoxem ia, raised blood vis- ↑RBF ↓↓RBF cosity, inhibition of sodium -potassium –activated ATPase and the – increased osm otic load to the distal tubule at a tim e of reduced Calcium oxygen delivery, the dem and for oxygen increases, resulting in antagonists cellular hypoxia and, eventually cell death. Additional factors Theophylline Net ↓O2 delivery Net ↑O2 consumption that contribute to the acute renal dysfunction of contrast-associ- ated nephropathy are the tubule obstruction that results from increased secretion of Tam m -H orsfall proteins and the liberation of reactive oxygen species and lipid peroxidation that accom pa- Cell injury ny cell death. As noted in the figure, calcium antagonists and theophylline (adenosine receptor antagonist) are thought to ↑TH protein ↑Intrarenal number act to dim inish the degree of vasoconstriction induced by con- of macrophages, T cells trast m edium. Stimulation of mesangium The clinical presentation of contrast-associated nephropathy involves an asym ptom atic increase in serum creatinine within 24 Tubular obstruction Superoxidase hours of a radiographic im aging study using contrast m edium , – – dismutase with or without oliguria. W e have recently reviewed the clinical outcom e of 281 patients with contrast-associated nephropathy according to the presence Reactive O species or absence of oliguric acute renal failure at the tim e of diagnosis. In the absence of oliguric acute renal failure Contrast associated nephropathy the serum creatinine value does not return to baseline in 24% of patients, approxim ately a third of whom require perm anent dialysis. Thus, this is not a benign condition but rather one FIGURE 11-22 whose defined risks are not only perm anent dialysis but also A proposed m odel of the m echanism s involved in radiocontrast death. GFR— glom erular filtration rate; RBF— renal blood flow; m edium –induced renal dysfunction. Based on experim ental m od- TH — Tam m H orsfall protein. Thus it is im portant to select the least invasive diagnostic proce- dure that provides the m ost inform ation, so that the patient can PREVENTION OF CONTRAST m ake an inform ed choice from the available clinical alternatives. ASSOCIATED NEPHROPATHY Since radiographic contrast im aging is frequently perform ed for diabetic nephropathy, congestive heart failure, or chronic renal failure, concurrent adm inistration of renoprotective Hydrate patient before the study (1. The correction of Use nonionic, iso-osmolar contrast media for patients at high risk (see Figure 11-21). Lim iting the total volum e of contrast m edium and using nonionic, isoosm olar FIGURE 11-23 m edia have proven to be protective for high-risk patients.