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Moreover purchase 4 mg coversyl with visa, the epileptic hippocampus is substantiallyreduced in size compared with the control purchase 4mg coversyl otc. C and D: High magnifica- tion of portions of the olfactoryfield of the entorhinal cortex from a patient with MTLE (C) and a control subject (D) generic coversyl 4mg on-line. Note the substantiallyreduced width of layers I to III of the entorhinal cortex of the patient with epilepsy buy generic coversyl 8mg on-line. Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy. Because pyramidal cells of layer III normally give portion of this six-layered parahippocampal structure. Pa- rise to the monosynaptic 'temporoammonic' pathway to tients frequently present with a characteristic pattern of neu- area CA1of the hippocampus (27), their degeneration in ronal loss and associated gliosis, with layer III being prefer- MTLE may lead to deafferentation-induced changes in hip- entially affected and layer II showing pronounced pocampal excitability, and such changes have indeed been disorganization and some cell loss (26) (Fig. Neuropathologic changes in layer 1846 Neuropsychopharmacology: The Fifth Generation of Progress II of the entorhinal cortex, the origin of the major input to the granule cells of the dentate gyrus (the 'perforant path'), may also contribute to hippocampal hyperexcitabil- ity in MTLE. Neuronal loss and gliosis in the amygdala are frequently seen in MTLE and often occur in conjunction with lesions in other parts of the limbic system (29,30). Although the pattern of cell loss has so far not been analyzed in great detail, degenerative events appear primarily to affect the ventromedial aspects of the lateral amygdaloid nucleus and the parvicellular region of the basal nucleus (31). Based on published studies, this relatively restricted damage not only impedes processing of sensory information in intraamygda- loid circuits, but may also account for the impairment of memory processing in MTLE by interrupting information FIGURE 127. Imaging studies illustrating changes in extrahip- flow to the hippocampal formation (31,32). MRI scans (A and C) and fluoro- It is likely that neuropathologic changes also occur in deoxyglucose PET scans (B and D) in a patient with left MTLE. The other areas that are connected to the reverberating seizure demarcations on the two sets of scans represent the co-registra- tion of the two techniques so comparable sites are illustrated in network underlying MTLE (33). A and B show changes in hippocampus (circled include the thalamus (34), have been shown to be atrophied in white in MRI, indicated with an arrow in the PET scan) and in patients, but the precise nature and distribution of the thalamus (outlined in black) with the medial dorsal nucleus indi- catedseparatelyinA. MRIdemonstrates atrophyin theleft hippo- degenerative changes, as well as their relation to the patho- campusand theleftmediodorsal nucleus,andPET showshypome- physiology of MTLE, have not been elucidated to date. The left brain hemisphere corresponds to the right side of the images. Chugani, Wayne IN VIVO IMAGING State University, Detroit, MI. These meth- the 1990s, magnetic resonance imaging studies also revealed ods have also been, and continue to be, of critical impor- shrinkage in other areas of the seizure circuit, namely, the tance for the generation and testing of hypotheses related to amygdala (38,39), the entorhinal cortex (40), and the thala- pathogenesis and disease progression. In the case of MTLE, mus (6), findings demonstrating that the extrahippocampal techniques such as computed tomography, measurements changes in tissue volume known to exist in many MTLE of regional glucose use and receptor densities by positron patients can be visualized noninvasively (Fig. Imaging test results are increasingly used for diagnostic purposes and, specifically, to provide guidance STUDIES IN EXPERIMENTAL ANIMALS for neurosurgical procedures. Kindling Improvements in the spatial resolution of most imaging techniques have made it possible to study regional brain Kindling, a phenomenon first described in 1969 (41), has abnormalities in MTLE with increasing accuracy. In early become a major research tool to study seizures involving studies, hypometabolism and decreases in cerebral blood the limbic system. In this model, a single site in the brain flow in the temporal lobe were demonstrated even when no is stimulated electrically with sufficient intensity to induce structural damage was detectable by computed tomography. With repeated focal stimulations for days or weeks, provide quantitative data adequately (8,35), but results ob- there is a gradual lengthening of the after-discharge, and tained by magnetic resonance imaging are remarkably in- behavioral seizures develop. Thus, using various modifica- behavior progresses to the point of a full convulsion. After tions of the technique, it became feasible to visualize a number of stimulations, the seizures reach a plateau of Chapter 127: Temporal Lobe Epilepsy 1847 consistent duration and behavioral severity, at which point models are commonly based on an inciting event of limbic the animal is considered fully kindled. The number of stim- status epilepticus that is precipitated by various methods, ulations required to achieve this plateau depends on several including the systemic administration of chemoconvulsants factors, such as the frequency and duration of focal stimula- (e. Studies of several limbic sites, as well lation of a limbic structure (hippocampus, perforant path, as comparisons of neocortical and subcortical regions, dem- amygdala) (51–53). In all these models, the animals recover onstrated that some extrahippocampal sites, for example, after status epilepticus and, after a latent period of weeks the amygdala, achieve the fully kindled state much faster to months, develop spontaneous seizures that continue in- than the hippocampus (43). First, seizures appear spontaneously and, certain subcortical structures, including the midline thala- like the seizures of human MTLE, have a clear predilection mus and the substantia nigra (44,45). This pattern suggests that The variable rates of kindling from different stimulation the seizures are likely to be under subcortical influence. Sec- sites suggest that some regions are more epileptogenic, that ond, as in the case of human MTLE, there is a latent period is, more able to generate and support seizure activity than during which a previously nonepileptic brain evolves into other sites. An alternative explanation is that the areas with one that generates recurring seizures. Third, the histopatho- more rapid rates of kindling are 'closer' to the pathways of logic changes in chronically epileptic animals, such as gliosis secondary generalization. This implies that seizure activity and neuronal loss in the hippocampus, amygdala, entorhinal spreads by gradual recruitment of adjacent cortex (similar cortex, and medial dorsal thalamus, closely resemble those to the classic jacksonian march), exemplified by the proposed seen in the human condition. Finally, the EEG patterns role of the perirhinal cortex as the major route from the and the locations of seizure onset are similar in human limbic system to the neocortex (46). However, this idea MTLE and in these animal models, a finding suggesting is confounded by the observation that seizures can appear similarities in the underlying pathophysiology (Fig. Taken together, these increasingly important for the study of limbic epilepsy. The findings therefore suggest the existence of a subcortical animals offer several important advantages, which largely 'control center,' for example, the midline thalamic region, offset the limitations of the rodent brain, that is, its small with direct connections to several of the limbic sites involved size and less developed cortical architecture. The availability of 'MTLE- cause drugs that prolong or abolish kindling acquisition like' animals also makes it possible to study the progression could ameliorate or prevent the development of chronic of events that eventually result in a chronic epileptic condi- epilepsy, that is, act as antiepileptogenic agents. Indeed, tion, that is, to assess the silent, latent period between status agents such as phenobarbital, carbamazepine, and several epilepticus and the first spontaneous limbic seizure. Finally, N-methyl-D-aspartate (NMDA)–receptor antagonists at- these animal models provide opportunities to test innovative tenuate the kindling rate, whereas other commonly used clinical interventions for the treatment and possible cure of antiepileptic compounds, such as phenytoin, do not have MTLE (54,55). This clinically relevant use of the kin- These models of limbic epilepsy have been exploited to dling model will eventually also provide a better definition test novel concepts related to the pathophysiology of of the molecular events that underlie the progressive length- MTLE. For example, hyperexcitable neurons, both projec- ening of seizure activity on repetitive stimulation. In some cases, the synaptically me- diated responses in these neurons show prolonged excitatory Animal Models of MTLE depolarizations with multiple superimposed action poten- The kindling model has been, and continues to be, valuable tials (23,56,57) (Fig. Underlying these profound for our understanding of the role of particular brain regions changes are multiple presynaptic and postsynaptic altera- in the generation and propagation of seizures. However, tions in neurotransmitter receptors and ion channels. Since the 1980s, the development of ani- in both inhibitory and excitatory receptors, namely GABA mal models with recurrent, spontaneous convulsions has and glutamate receptors, contribute to the abnormal physi- therefore become a major focus of epilepsy research. These changes are necessarily complex be- 1848 Neuropsychopharmacology: The Fifth Generation of Progress FIGURE 127. Seizures in human MTLE and in rat models of MTLE: illustrations of altered neu- ronal physiology. Chronic epilepsy in animals was induced by prolonged electrical stimulation or chemoconvulsants (see text). A: Bilateral recordings from hippocampus (LH, RH) and amygdala (LA, RA) in rat (A1) and human (A2). Both sites are involved at the onset, a finding suggesting a synchronizing pulse from an external site. The human recording shows a later but regionally simultaneous onset on the left hemisphere. This time difference is not seen in rats, probablyas a result of stronger interhemispheric connections. B: Intracellular recordings from hippocampal and amygdalar neurons in normal and epileptic rats. C: Intracellular recordings from the entorhinal cortex of epileptic rats, also illustrating the prolonged depolarizations and multiple superimposed action potentials. Overall, this figure emphasizes the changes throughout the limbic system in nonhippocampal regions. In addition, the models also involve simplicity of the new circuit and the easily visualized ana- many other biochemical changes in one or more parts of tomic change (64). Because the animal models of MTLE the limbic seizure network. This ever-increasing list includes show extensive neuronal loss in multiple brain areas, it is ions, enzymes, hormones and their receptors, and a host quite likely that seizure-related synaptic and circuit rear- of other chemical entities.

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Textbooks are devoted to the field cheap coversyl 4 mg on line, and even to particular aspects of the field generic coversyl 4 mg overnight delivery. In an earlier chapter cheap coversyl 8 mg without a prescription, mental health (of adults) was identified as a utopian/optimal state 8 mg coversyl overnight delivery. By contrast, the stated aim of the DOP is to provide a guide to the treatment of mental disorder, rather than a guide to the achievement/maintenance of mental health. With children, however, the distinction between mental health and a mental disorder is less clear, and child psychiatrists deal with deviations from mental health in addition to mental disorder. Child psychiatric disorders must be viewed in the context of normal development (a process of change and increasing complexity). Many disorders are identified as failure to reach developmental milestones. Students need to be aware of the stages of normal development from an appropriate source (only a brief introduction is presented in the following section). Child psychiatric disorders must also be viewed in the context of the family, social and cultural setting. Environmental factors are important in adult psychiatry; but as children are dependent, lack certain capacities and perspectives and are vulnerable, these factors assume even greater importance. In child psychiatry (in contrast to adult psychiatry) it is rare for the “patient” to initiate contact with the psychiatric service; first contact is usually made by a parent or an educational or welfare authority. It is usually important to speak at length with the referrer and the family. Not only do family members provide much of the history, the family is the medium in which the child exists and will continue to grow (and hopefully, recover). The manner in which the family operates and the place/role of the child within the family must be understood. The manner in which the family functions may be part of the problem, and aspects of family functioning may need to be modified. Thus, the family may be a significant therapeutic modality, and must be involved and kept “on side” (wherever possible). Normal development We begin life with little awareness. We grow into fully functioning adults: walking, standing on wave-catapulted surfboards, learning and reading the newspaper, negotiating, forming relationships and providing love and guidance for our own babies. The rate of change (physical growth, skill acquisition, intellectual and emotional development) is greatest during childhood and adolescence. The basics of physical and social development of the child include: 0-6 months: rolls over, smiles and laughs, passes objects hand to hand, places objects in the mouth, vocalises syllables. Middle childhood: schooling, peer group activities, developing autonomy. Adolescence: increasing independence, autonomy and peer group activities. All describe “stages” and tasks/skills which must be mastered during these stages in order to achieve smooth progress through to functional adulthood. No one perspective provides a complete account, and different concepts are helpful is dealing with different patients (or disorders). Freud (Austrian; 1856-1939) provided the first description of “psychosexual development”. His theory of personality development focused on the effects of the sexual pleasure drive upon the mind. He believed that at particular points along the developmental path a body part is particularly sensitive to sexual, erotic stimulation – the erogenous zones: mouth, anus, genitals. The stages the child passes through are the oral (0-18 months), anal (18-36 months), phallic (3-6 years), latency (6 years to puberty) and genital (puberty and beyond). He taught that children are unable to undertake certain tasks until they are psychologically mature enough to do so. Erickson (Swede; 1833-1887) described himself as a Freudian. However, rather than focus on the basic drives (as did Freud), Erickson emphasised the importance of the ego (or executive function of the mental apparatus) in personality development. Successful completion (resolution of a conflict/task) leads to a favourable result (virtue): Stage One (0-1 years) task: trust vs. Attachment (the making of strong affectional relationships with others) is a characteristic of human beings, and many other species. Stable relationships are a source of enjoyment and security, and separation, loss or threatened loss of a relationship is a source of anxiety, anger, sadness and depression. Attachment Theory is the dominant current theory in the study of infant and toddler behaviour and is used in the field of infant mental health diagnosis and treatment. It is based on the attachment work of Bowlby and Ainsworth, among others. The Circle of Security uses “The Strange Situation” paradigm (Ainsworth, 1969) in the assessment of attachment and early psychological difficulties. The Strange Situation is a series of contrived settings which allows staff to observe attachment relationships between the child and caregivers. The child is observed playing for 20 minutes while caregivers and strangers enter and leave the room. Mother sits quietly on a chair, responding if the infant seeks attention 3. A stranger enters, talks to the mother then gradually approaches the infant with a toy. The stranger leaves the infant playing unless he/she is inactive. The stranger then tries to interest the infant in toys. If the child becomes distressed this episode is ended 5. Mother enters and waits to see how the infant greets her. The stranger leaves quietly and the mother waits until the baby settles, and then she leaves again 6. This episode is curtailed if the infant is distressed 7. Reunion behaviour is noted and the situation is ended. The amount the child explores (playing with new toys) and engages, and B. Based on these observations the attachment style is categorized/diagnosed, and management implications are decided. Attachment therapy practitioners explain to parents the needs of the child, the importance of security and the need for the opportunity to explore, and help them to develop good parenting skills. With the advantage of good parenting the child has the opportunity to develop in a health manner. In the top half the child is feeling safe and secure and there is a natural tendency to explore the world. The role of the parent is to allow safe exploration. At times the child needs the parent to watch-over without taking-over. In the bottom half the child is tired, frightened or no longer interested in exploring and needs to return to safety. DSM-5 The DSM5 involves a number of changes to the arrangement of topics/disorders of interest to Child Psychiatry. A glance confirms the complexity of modern child psychiatry. Intellectual Disabilities Communication Disorders Language disorder, Speech Sound Disorder, Social Communication Disorder Autism Spectrum Disorder With or without intellectual impairment or language impairment Pridmore S.

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Community patterns of prehensive assessment of mortality and disability from diseases best 8mg coversyl, inju­ posttraumatic stress disorders coversyl 8mg free shipping. J Nerv Ment Dis 1989;177: ries buy coversyl 4 mg with visa, and risk factors in 1990 and projected to 2020 order coversyl 8 mg. Quantifying the burden of disease: the technical matic Stress Disorder in the community: the 1996 Detroit Area basis for DALYs. The chronic associa­ den of anxiety disorders in the 1990s. J Clin Psychiatry 1999; tion between medical conditions and work impairment. Caring and doing for others: social responsibility in the 9. Psychiatric disorders in America: rhe domains of family, work, and community. Chicago: University of Epidemiologic Catchment Area Study. National Institute of ity of life and activity limitation—eight states, 1995. MMWR Mental Health Diagnostic Interview Schedule: its history, charac­ 1998;47:134–139. J Affective epidemiology of major depression and bipolar disorder. Posttraumatic stress disorder: the burden to the indi­ 13. In: Tsuang able for use in conjunction with different diagnostic systems and MT, Tohen M, Zahner GEP, eds. Textbook in psychiatric epide­ in different cultures. The World Health Organization International Con­ 35. In: Wetz­ sortium in Psychiatric Epidemiology (ICPE): initial work and ler S, Sanderson WC, eds. Treatment strategies for patients with future directions—the NAPE lecture 1998. WHO International Consortium in Psychiatric Epidemiology. Cross-national comparisons of the prevalences and correlates of 37. Comparing pri­ mary and secondary generalized anxiety disorder in a long-term mental disorders: an ICPE survey. Is the course of panic America: the Epidemiologic Catchment Area Study. Chronicity in posttrau­ month prevalence of DSM-III-R psychiatric disorders in the matic stress disorder (PTSD) and predictors of course of comor­ United States: results from the National Comorbidity Survey. Issued by funding/sponsoring agency: Office of Vital Statistics. Arch Gen Death rates for 282 selected causes by 5-year age groups, color, and Psychiatry 1994;51:355–364. Impairment in pure MD: National Center for Health Statistics; Centers for Disease and comorbid generalized anxiety disorder and major depression Control; Public Health Service. Psychiatric disorders and 15-month mortality Robins LN, Regier DA, eds. Psychiatric disorders in America: the in a community sample of older adults. Am J Public Health 1989; Epidemiologic Catchment Area Study. Setting diagnostic thresholds disorders on labor market outcomes. Ind Labor Relat Rev 1997; for social phobia: considerations from a community survey of 51:64–81. Posttraumatic stress orders and male socioeconomic status. Social Sci Res 1998;27: disorder in the National Comorbidity Survey. Posttraumatic stress of psychiatric disorders, I: educational attainment. Am J Psychia­ disorder in the community: an epidemiological study. Post-traumatic stress disorder of psychiatric disorders, II: teenage parenthood. The National Comorbidity Survey of the United of psychiatric disorders: III. Five years after: the long-term effects of comorbid anxiety disorders in primary care outpatients. New York: Russell Sage Foundation, Med 1996;5(1):27–34. New York: Russell a review of the medical and psychiatric literature. Comorbid anxiety employment of welfare recipients [discussion paper]. Madison, disorder and the functioning and well-being of chronically ill WI: University of Wisconsin-Madison; Institute for Research on patients of general medical providers. Psychological factors affecting medical conditions: and the functional capacity to work. The impact of psychiatric disorders on 1995:187–192. Venlofaxine XR in the treat­ American Psychiatric Press, 1990:205–230. Patterns and predictors of tion and suicide attempts in panic disorder and attacks. N Engl treatment contact after first onset of psychiatric disorders. Psychiatric disorder of lifetime suicide attempts in the National Comorbidity Survey. Distressed high utilizers other psychiatric disorders in the National Comorbidity Survey. Effects of psychological distress and stance comorbidities in the ICPE surveys]. Psychiatria Fennica psychological well-being on use of medical services. The economic DSM-III-R major depressive disorder in the general population: burden of depression in 1990. J Clin Psychiatry 1993;54: results from the US National Comorbidity Survey. Generalized anxiety and mixed anxiety-depres­ workplace: an economic perspective. In: Feighner JP, Boyer WF, sion: association with disability and health care utilization. Selective serotonin re-uptake inhibitors: advances in basic re- Psychiatry 1996;57:86–91. TALLMAN JAMES CASSELLA JOHN KEHNE Drugs to reduce anxiety have been used by human beings conditions, including anxiety and depression (3). One of the first anxiolytics and one between CRF and depression is particularly strong, as nu- that continues to be used by humans is ethanol. A number of other drugs including the barbiturates CRF, elevated plasma cortisol, and a blunted ACTH re- and the carbamates (meprobamate) were used in the first sponse following intravenous CRF. Successful antidepres- half of the 20th century and some continue to be used sant treatment was shown to have a normalizing effect on today.

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In a 1 1 recent study of 60 patients with acute renal failure buy coversyl 4 mg with mastercard, a percutaneous 0 0 renal biopsy yielded a pathologic diagnosis in 13% that was not 1 2 3 4 5 6 7 8 expected clinically [154] 4 mg coversyl with amex. Day Renal Disease in Patients Infected with Hepatitis and Human Immunodeficiency Virus 7 safe 8 mg coversyl. Rao and Friedm an [155] com pared the course of 146 ACUTE RENAL FAILURE patients with severe acute renal failure (serum creatinine >6 m g/dL) infected with H IV with a group of 306 contem poraneous persons not infected with H IV but with equally severe acute renal failure generic coversyl 8 mg visa. The patients infected with H IV were younger than those in the HIV Non-HIV group not infected (m ean age 38. O ver 80% of patients in each group Conservative 20 (14%) 42 (14%) recovered renal function when conservative therapy alone was sufficient. W hen dialysis Recovered 85% 83% NS intervention was needed, it was not initiated m ore often in the group with H IV than in the Needing dialysis 126 264 control group (42% and 24% , respectively; P<0. In those patients in whom dialysis Not initiated 42% 22% 0. O verall, the m ortality in Initiated 73 207 patients with severe acute renal failure was not significantly different in those with H IV Recovered 56% 47% NS infection from those in the group not infected with H IV (im m ediate m ortality, 60% and 56% , respectively; m ortality at 3 m onths, 71% and 60% , respectively). FIGURE 7-22 NEPHROPATHIES Nephropathies associated with HIV. The literature refers to the glomerulosclerosis associated ASSOCIATED W ITH with human immunodeficiency virus (HIV) as HIV-associated nephropathy. However, HIV- HUM AN IM M UNODEFICIENCY associated nephropathies may include a spectrum of renal diseases, including HIV-associated VIRUS INFECTION glomerulosclerosis, HIV-associated immune-complex glomerulonephritis (focal or diffuse proliferative glomerulonephritis, immunoglobulin A nephropathy) and HIV-associated hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Diffuse Focal segmental or global glomerulosclerosis mesangial hyperplasia and minimal change disease also may be associated with HIV, particu- larly in children. Therefore, the nomenclature of HIV-associated nephropathies should be Diffuse and global mesangial hyperplasia amended to list the associated qualifying histologic feature [156]. All types of glomeru- Minimal change disease lopathies have been observed in patients with HIV-infection. Their prevalence and severity Others: vary with the population studied. Focal segmental or global glomerulosclerosis is most preva- Immune-complex glomerulopathies lent in black adults. In whites, proliferative and other types of glomerulonephritis predomi- Hemolytic uremic syndrome, thrombotic nate. In children with perinatal acquired immunodeficiency syndrome, glomerulosclerosis, thrombocytopenic purpura diffuse mesangial hyperplasia, and proliferative glomerulonephritis are equally prevalent. Thus, concern existed Glomerulosclerosis that this entity m erely represented the older heroin nephropathy Diff. H owever, in a M iam i- 75 based population of adult non-IV drug users with glomerular disease and H IV infection, 55% of Caribbean and Am erican blacks had severe glom erulosclerosis, 9% had m ild focal glom erulosclerosis, 50 and 27% had diffuse m esangial hyperplasia. In contrast, two of 12 (17% ) whites had a m ild form of focal glom erulosclerosis, 75% had diffuse m esangial hyperplasia, and none had severe glom eru- 25 losclerosis. These m orphologic differences were reflected in m ore severe clinical presentations, with blacks m ore likely to m anifest proteinuria in the nephrotic range (>3. W hites often had Caribbean blacks American blacks W hites (n=22) (n=11) (n=12) proteinuria under 2 g/24 h and serum creatinine values less than 2 m g/dL [162]. In blacks, glom erulosclerosis has been described in all groups at risk for HIV infection, including IV drug users, homo- FIGURE 7-23 sexuals, patients exposed to heterosexual transmission or to contami- Glom erulosclerosis associated with H IV. In the United States, H IV- nated blood products, and children infected perinatally [163,164]. This entity initially was consid- striking predom inance in blacks independent of IV drug abuse ered with skepticism because it was not seen in San Francisco, [165]. Racial factors explain the absence of H IV-associated where m ost patients testing seropositive were white hom osexuals glom erulosclerosis in whites and Asians. In N ew York, patients with glom erulosclerosis were racial predilection is unknown. The onset of the October 1985: A dockworker until 3 months before admission, when nephropathy is often abrupt, with uremia and Viral syndrome. He massive nonselective proteinuria (sometimes nine, 0. These fulminant December 1986: periorbital and trace ankle edema, interstitial pneu- monia, and diffuse adenopathies. Serum creatinine lesions may present as acute renal failure in Fever, fatigue, cough. In other used intravenous drugs; 11-cm, echogenic kidneys neys. Renal biopsy showed focal segmental glomeru- patients, minimal proteinuria and azotemia at February 1987: losclerosis. Lymph node biopsy showed presentation increase insidiously over a period 3+ edema. This patient returned to of several months until a nephrotic syndrome tinine, 11. Hypertension and glomerulosclerosis peripheral edema may be absent even in the May 1987: context of advanced renal insufficiency or 100 lbs; patient died after 3 months of hemodialysis severe nephrotic syndrome. PATHOLOGIC FEATURES OF GLOM ERULOSCLEROSIS ASSOCIATED W ITH HUM AN IM M UNODEFICIENCY VIRUS INFECTION Collapsed glomerular capillaries Visceral glomerular epitheliosis Microcystic tubules with variegated casts Focal tubular simplification Interstitial lymphocytic infiltration Endothelial reticular inclusions FIGURE 7-26 Pathologic features of glom erulosclerosis. N one of the features list- FIGURE 7-25 ed is pathognom onic. The concom itant presence of glom erular and Ultrasonography of a hyperechogenic 15-cm kidney in a patient tubular lesions with tubuloreticular inclusions in the glom erular with H IV-associated glom erulosclerosis, nephrotic syndrom e, and and peritubular capillary endothelial cells, however, is highly sug- renal failure. Renal Disease in Patients Infected with Hepatitis and Human Immunodeficiency Virus 7. M icrograph of a m ore FIGURE 7-27 advanced stage of glom erulosclerosis with large hyperplastic viscer- Glom erulosclerosis. M icrograph of segm ental glom erulosclerosis al epithelial cells loaded with hyaline protein droplets, interstitial with hyperplastic visceral epithelial cells (arrows). FIGURE 7-29 FIGURE 7-30 Collapsing glom erulosclerosis. M icrograph of global collapsing Dilated m icrocystic tubules. M icrograph of m assively dilated m icro- glom erulosclerosis. In the cystic tubules filled with variegated protein casts adjacent to nor- sam e patient, norm al glom eruli, glom eruli with segm ental sclerosis, m al-sized glom eruli. The and glom eruli with global sclerosis m ay be found [172]. The tubulointerstitial changes likely play an im portant role in the pathogenesis of the renal insufficiency and offer one explanation for the rapid decrease in renal function. M icrograph of diffuse m esangial hyperplasia in a child with perinatal AIDS and nephrotic syndrom e. Both diffuse and global m esangial hyperplasia are identified in 25% of children with perinatal AIDS and protein- uria. The characteristic m icrocystic tubular dilations and the kidney enlargem ent of glom erulosclerosis associated with hum an im m un- odeficiency virus infection are absent in patients with diffuse m esan- gial hyperplasia. M icrograph of tubuloreticular cytoplasmic inclusions in glomerular endothelial cell. The latter are virtually diagnostic of nephropathy associated with HIV infection, provided systemic lupus erythematosus has been excluded. On immunofluo- rescent examination, findings in the glomeruli are nonspecific and similar in HIV-associated glom erulosclerosis and idiopathic focal segm ental glom erulosclerosis. These findings consist largely of immunoglobulin M and complement C3 deposited in a segmental granular pattern in the m esangium and capillaries. The sam e deposits also occur in 30% of patients with AIDS without renal disease [134,163,167]. FIGURE 7-33 HIV infection Possible pathogenic m echanism s of glom erulosclerosis associated with HIV infection.

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