By O. Ramon. Pacific States University.
W ilkins RG buy cialis 20 mg low cost, Faragher EB: Acute renal failure in an intensive care unit: Proteinkatabolism us cheap cialis 10 mg with amex, M ediatorsubstanzen und Prognose des akuten Incidence, prediction and outcom e. N ierenversagens [H abilitation-Thesis], M edical Faculty Technical 27. Firth JD: Renal replacem ent therapy on the intensive care unit. Yang VC, Fu Y, Kim JS: A potential throm bogenic hem odialysis m em - 29. Kierdorf H : Continuous versus interm ittent treatm ent: Clinical results branes with im paired blood com patibility. Jakob SM , Frey FJ, Uhlinger DE: Does continuous renal replacem ent 42. N ephrol D ial filtration for the treatm ent of congestive heart failure. M ehta RL: Acute renal failure in the intensive care unit: W hich out- 43. Drum l W : Prophylactic use of continuous renal replacem ent therapies com es should we m easure? H um es H D, M ackay SM , Funke AJ, Buffington DA: The bioartificial nous hem ofiltration. Anasth Intensivther N otfallm ed 1986, renal tuble assist device to enhance CRRT in acute renal failure. De Broe he kidneys are susceptible to toxic or ischemic injury for sever- al reasons. Thus, it is not surprising that an impressive list of Texogenous drugs and chemicals can cause clinical acute renal failure (ARF). On the contrary, the contribution of environmental toxins to ARF is rather limited. In this chapter, some of the most com- mon drugs and exogenous toxins encountered by the nephrologist in clinical practice are discussed in detail. The clinical expression of the nephrotoxicity of drugs and chemi- cals is highly variable and is influenced by several factors. Among these is the direct toxic effect of drugs and chemicals on a particular type of nephron cell, the pharmacologic activity of some substances and their effects on renal function, the high metabolic activity (ie, vul- nerability) of particular segments of the nephron, the multiple trans- port systems, which can result in intracellular accumulation of drugs and chemicals, and the high intratubule concentrations with possible precipitation and crystallization of particular drugs. ACE— angiotensin-converting enzym e; N SAID— nonsteroidal anti-inflam - m atory drugs; H gCl2— m ercuric chloride. S1 Cortex Sites of renal damage S2 ACE inhibitors NSAIDs Aminoglycosides S Acyclovir 1 Cisplatinum S HgCl2 3 S2 Lithium S Ischemia Outer 3 stripe Vulnerability of the kidney Inner stripe Important blood flow (1/4 cardiac output) High metabolic activity Largest endothelial surface by weight M ultiple enzyme systems Inner Transcellular transport medula Concentration of substances Protein unbinding High O2 consumption/delivery ratio in outer medulla Renal Injury Due To Environmental Toxins, Drugs, and Contrast Agents 11. FIGURE 11-2 Drugs and chem icals associated with acute renal failure. Binding + - + - - - Lysosomal phospholipidosis ABOVE * threshold: lysosomal 3. Adsorptive swelling, BELOW disruption * threshold: pinocytosis or leakage exocytosis shuttle 4. Lysosomal trapping * and storage * Regression of * drug-induced changes Cell necrosis * Aminoglycoside regeneration Hydrolase * Toxins FIGURE 11-3 Renal handling of am inoglycosides: 1) glom erular filtration; After charge-m ediated binding, the drug is taken up into the cell 2) binding to the brush border m em branes of the proxim al in sm all invaginations of the cell m em brane, a process in which tubule; 3) pinocytosis; and 4) storage in the lysosom es. W ithin 1 hour of injection, the N ephrotoxicity and otovestibular toxicity rem ain frequent side drug is located at the apical cytoplasm ic vacuoles, called endocy- effects that seriously lim it the use of am inoglycosides, a still im por- totic vesicles. These vesicles fuse with lysosom es, sequestering the tant class of antibiotics. Am inoglycosides are highly charged, poly- unchanged am inoglycosides inside those organelles. They are not m etabolized but are elim inated unchanged glycosides electrostatically attached to anionic m em brane phospho- alm ost entirely by the kidneys. Am inoglycosides are filtered by the lipids interfere with the norm al action of som e enzym es (ie, phos- glom erulus at a rate alm ost equal to that of water. In parallel with enzym e inhibi- the lum inal fluid of proxim al renal tubule, a sm all but toxicologi- tion, undigested phospholipids originating from the turnover of cell cally im portant portion of the filtered drug is reabsorbed and m em branes accum ulate in lysosom es, where they are norm ally stored in the proxim al tubule cells. The overall result is lysosom al phospholipidosis due to glycosides into proxim al tubule cells involves interaction with nonspecific accum ulation of polar phospholipids as “m yeloid bod- acidic, negatively charged phospholipid-binding sites at the level ies,” so called for their typical electron m icroscopic appearance. Lysosomes (large arrow) contain dense lamellar and concentric struc- tures.
As the first rec- What then is the importance of 22q11 and VCFS in the ognized cohort of children with VCFS was followed into etiology of schizophrenia as a whole? Early tients with schizophrenia discount 5 mg cialis with mastercard, two were found to have a 22q11 reports suggested that psychiatric disorders had developed deletion order cialis 2.5mg mastercard. In contrast, when subjects with schizophrenia were in more than 10% of the cohort, which mostly resembled selected for the presence of clinical features consistent with chronic schizophrenia with paranoid delusions, although VCFS, 22q11 deletions were identified in 20% to 59% of operational criteria were not used (147). These findings suggest that a small propor- study of teenagers (age 17 years) in which DSM-III-R crite- tion of cases of schizophrenia may result from deletions of ria were used, Pulver et al. The question of whether genetic depression, and 14% had obsessive-compulsive disorder. As sample of 15 children and 10 adults, four (16%) had psy- we have seen, the results of some linkage studies suggest chotic symptoms and 16 (64%) met DSM-III-R criteria for the presence of a schizophrenia susceptibility locus on 22q. Although none However, the linkage findings tend to point telomeric to had schizophrenia, the two oldest members of their patient the VCFS region (86,157). Nevertheless, modest evidence cohort (ages 29 and 34 years) both had schizoaffective dis- for linkage to the VCFS region has also been claimed (90, order. It remains possible lence and nature of psychopathology in adults with VCFS, that the relationship between VCFS and 'typical' schizo- rather than rely on clinical diagnosis, Murphy and col- phrenia is less direct, with little common ground between leagues (149) recently evaluated 50 cases with a structured the genetic and neurodevelopmental mechanisms involved clinical interview to establish a DSM-IV diagnosis. Fifteen but with convergence on identical or at least similar psycho- patients with VCFS (30%) had a psychotic disorder, with pathologic syndromes. Another important question concerns the factors that In addition, six (12%) had major depression without psy- determine whether schizophrenia will develop in a person chotic features. They were unable to replicate the findings with VCFS. When adults with VCFS were tested with a of Papolos and colleagues (146) of a high prevalence of quantitative measure of schizotypy, the patients with psy- bipolar spectrum disorders in VCFS. However, these work- chosis had the highest scores (149). However, perhaps of ers studied a small sample that included few adults, and in greater interest, those without psychosis had intermediate 680 Neuropsychopharmacology: The Fifth Generation of Progress scores in comparison with controls (149). If schizotypy is are clinical symptoms—so-called intermediate phenotypes a trait marker for increased liability to psychosis, this sug- or endophenotypes. Work in this area is developing fast; for gests that the majority if not all of those with 22q11 dele- example, candidate trait markers for schizophrenia include tions are at increased risk for psychosis, but that other ge- schizotypal personality traits, measures of cognitive process- netic or environmental factors are required for this risk to ing, brain evoked potentials, and abnormalities in eye move- be expressed. The genetic loci involved may reside elsewhere ments (163). It is also hoped that advances in brain imaging in the genome and include those involved more widely in will lead to the identification of genetically valid trait mark- psychosis, or lie within 22q11. However, it seems unlikely that these phenotypes will does not appear to be related to the size of the deletion provide a rapid solution to the problem. However, it is possible that susceptibility to psychosis to ensure that the measures used are stable and determine reflects allelic variation of a hemizygous gene or genes within the extent to which they are affected by state. The gene encoding catechol-O-methyltransfer- be of use in gene mapping, such measures will have to be ase (COMT), an enzyme involved in the catabolism of cate- practicably applied to a sufficient number of families or cholamine neurotransmitters, maps to the VCFS region and unrelated patients. Third, we will need to ensure that the is therefore an obvious candidate for influencing the expres- traits identified are highly heritable, which will itself require sion of psychosis in VCFS probands. This gene exists in a return to classic genetic epidemiology and model fitting. However, concerned with enhancing the traditional categoric ap- Murphy and colleagues (149) found no evidence for an proach to defining psychiatric disorders by identifying ge- association between the allele for low-activity COMT and netically valid phenotypes that can be measured quantita- either schizophrenia or schizotypy in patients with VCFS. These can be used in quantitative trait locus approaches to gene mapping. Work in this area has begun but still faces problems, particularly those relating to the FUTURE DIRECTIONS confounding influence of state-related effects. Perhaps the best hope of taking account of the complexity and heteroge- Refining the Phenotype for Molecular neity of the schizophrenia phenotype comes from new Genetic Studies methods of analysis in which aspects of the phenotype can The effectiveness of molecular genetic studies depends on be entered as covariates in linkage analyses (164). Perhaps if we were better at defining phenotypes, we would be better Genome-wide Association Studies at finding genes. It is worth reiterating at this point that the commonly used diagnostic criteria define phenotypes In recent years, interest has increased in the possibility of with high heritability. In principle, therefore, it should be systematic, genome-wide association studies (109,165). However, perhaps genetic validity been fueled by the fact that the most abundant form of could be improved by focusing on aspects of clinical varia- genetic variation, the single-nucleotide polymorphism, is tion, such as age at onset or symptom profiles, or by identi- usually bi-allelic and potentially amenable to binary, high- fying biological markers that predict degree of genetic risk throughput genotyping assays such as microarrays (so-called or define more homogeneous subgroups.
The effects of chronic eliminates psychomotor vigilance deficits from sleep inertia purchase 2.5 mg cialis otc. J effects on daytime alertness ad nighttime recovery cheap 5 mg cialis with amex. Effects of partial sleep book of human performance,vol 2. A1 adenosine receptor stimulation mimics sleep length. Minimal sleep to maintain performance: the search 1993;22:4. Effect of caffeine on physiologic sleep tendency Why we nap: evolution,chronobiology,and functions of polyphasic and ability to sustain wakefulness at night. Chronic restriction of sleep ogy 1994;113(3–4):411–421. The use of prophylactic naps and but not subjective sleepiness. The pharmacological basis activity in major depression. Modafinil: the unique properties of a new vation induces opposite effects on mood states in depressed and stimulant. Letter: sleep deprivation and thyroid on nocturnal activity in monkeys (Macaca mulatta) after acute hormones. Nonpharmacologic treatments for in phetamine induced wakefulness, a comparative pharmacological somnia. Inhibitory effects of the psychoactive drug fects of progressive and hypnotic relaxation on insomnia. J Ab modafinil on gamma-aminobutyric acid outflow from the cere norm Psychol 1973;82(1):153–158. Possible in- Chapter 130: Sleep Loss and Sleepiness 1905 volvement of 5-hydroxytryptamine mechanisms. Central alpha 1-adrenergic stimulation in relation 113. Prediction of intentional and uninten 1995;10:167–176. Use of bright light to treat maladaptation normal and abnormal. Sustaining performance during continuous opera 104. International ment: strategic naps in operational settings. J Sleep Res 1995; Conference Proceedings on Managing Fatigue in Transporta 4(S2):62–66. Models of circadian and homeostatic regulation feine as countermeasures for shift work related sleepiness and of human performance and alertness. Commercial Motor Vehicle Driver Fatigue and Alertness Study. Department of Trans their alleviation by melatonin. Field testing a prototype drowsy driver detection and to phase shift. The role of actigraphy in ence on Enhancing Commercial Motor Vehicle Driver Vigi evaluation of sleep disorders. Correlation of steering behavior with heavy truck driver Sleep 1995;18(4):285–287. Proceedings of the Technological Conference on En 110. Sleep 1999;22(8): hancing Commercial Motor Vehicle Driver Vigilance, Ameri 1110–1117. Commercial Motor Vehicle Driver Vigilance, American Truck 112.
Ying CY 20 mg cialis amex, Tifft CP buy cheap cialis 2.5mg on-line, Gavras H , Chobanian AV: Renal revascularization hypertension and renal insufficiency: trends in m edical com orbidity in the azotem ic hypertensive patient resistant to therapy. N ovick AC, Pohl M A: Atherosclerotic renal artery occlusion extend- 18. In ing into branches: successful revascularization in situ with a branched H ypertension. The production of persistent elevation of systolic blood causing end-stage renal disease, incidence, clinical correlates, and pressure by means of renal ischemia. Am J Kidney D is 1994, M orris GC Jr, DeBakey M E, Cooley M J: Surgical treatm ent of renal failure 24:622–639. Appel RG, Bleyer AJ, Reavis S, H ansen KJ: Renovascular disease in older N ovick AC, Ziegelbaum M , Vidt DG, et al. Page IH : The production of persistent arterial hypertension by cellophane J Am Soc N ephrol 1998, 9:252–256. Adv N ephrol N ecker H osp correlation of renal arterial disease. Pohl M A, Novick AC: Natural history of atherosclerotic and fibrous renal Novick AC, Straffon RA, Stewart BH, et al. Goncharenko V, Gerlock AJ Jr, Shaff M I, H ollifield JW : Progression of Novick AC, Stewart R: Use of the thoracic aorta for renal revascularization. Hollenberg NK: M edical therapy of renovascular hypertension: efficacy and Textor SC: Renovascular hypertension. Curr O pin N ephrol H yperten safety of captopril in 269 patients. Pohl M A: M edical m anagem ent of renovascular hypertension. In Renal W orking Group on Renovascular H ypertension: Detection, evaluation, and Vascular D isease. Arch Intern M ed London: W B Saunders; 1996, 339–349. H ypertension stenoses with vascular endoprostheses after unsuccessful balloon 1989, 14:247–257. H ypertension stenting on progression of renovascular renal failure. H ypertension 1989, Pickering TG, Herman L, Devereux RB, et al. Angioplastie (EM M A) Study Group: Blood pressure United States Renal Data System Coordinating Center: Incidence and causes outcom e of angioplasty in atherosclerotic renal artery stenosis: of treated ESRD. Bethesda: USRDS Coordinating Textor SC: Revascularization in atherosclerotic renal artery disease Center; 1994:43–54. W einberger he adrenal gland is involved in the production of a variety of steroid hormones and catecholamines that influence blood Tpressure. Thus, it is not surprising that several adrenal disorders may result in hypertension. M any of these disorders are potentially curable or responsive to specific therapies. Therefore, identifying adrenal disorders is an important consideration when elevated blood pressure occurs suddenly or in a young person, is severe or difficult to treat, or is associated with manifestations suggestive of a secondary form of hypertension. Because these occurrences are relatively rare, it is necessary to have a high index of suspicion and understand the pathophysiology on which the diagnosis and treatment of these problems is based. Three general forms of hypertension that result from excessive produc- tion of mineralocorticoids, glucocorticoids, or catecholamines are reviewed in the context of their normal production, metabolism, and feedback systems. The organization of this chapter provides the background for understanding the normal physiology and pathophysiologic changes on which effective screening and diagnosis of adrenal abnormalities are based. Primary aldosteronism Autonomous hypersecretion Increased renal sodium and Extracellular fluid volume of aldosterone (hyperminer- water reabsorption, expansion, hypokalemia alocorticoidism) increased urinary (? A cross section of the norm al adrenal Zona before (left) and after (right) stim ulation with adrenocorticotropic glomerulosa horm one (ACTH ). The adrenal is organized into the outer adrenal cortex and the inner adrenal m edulla. The outer adrenal cortex is com posed of the zona glom erulosa, zona fasciculata, and zona reticularis. The zona glom erulosa is responsible for produc- Zona tion of aldosterone and other m ineralocorticoids and is chiefly fasciculata under the control of angiotensin II (see Figs.