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Furthermore cheap levothroid 200 mcg amex thyroid symptoms choking, while patients with lower disease and treatment-related adverse events (e purchase 200 mcg levothroid mastercard thyroid jaw clenching. Lastly cheap 100 mcg levothroid fast delivery thyroid cancer emedicine, while patients who undergo destination therapy implantation are typically 45 buy 50 mcg levothroid visa thyroid gland assessment. Patients report that most symptoms of self-care, usual activities, anxiety/depression, and heart failure (e. However, at 6 months post- eral edema) abate relatively soon afer implant, implant, female patients report signifcantly more while other symptoms (e. Patients ofen returned to home wherein improvement among all age groups was management, work, and leisure activities [20]. Local support groups [26] or credible, their sense of responsibility for equipment/sup- well-established, online caregiver support groups plies and care of the patient. Two types of caregiver burden were identifed: the burden of making the decision to move forward 45. Palliative care new lifestyle as a caregiver, positive self-talk, and goals of care include relief of sufering, enhance- faith and religiosity [25]. Palliative care consultation is indicated for Important components of a caregiver assessment patients (e. Institute of Medicine Committee on Quality of Health allowing patients to simply succumb to their Care in America (2001) Crossing the quality chasm: a new health system for the 21st century. Administration of anesthet- Cardiovasc Qual Outcomes 7:374–380 ics, analgesics, and anxiolytics, at appropriate 6. Eur Respir the device, without initiating alarms, which can J 24:200–205 cause distress for all present. Long-term emotional sequelae in patients tination therapy mechanical circulatory support is and spouses. J Heart Lung Transplant 26:384–389 similar for older and younger patients: analyses from 24. J Heart Lung Transplant 34:213–221 Emotional experiences of caregivers of patients with 18. Prog Transplant 20:142–147 Risk assessment and comparative efectiveness of left 25. Bunzel B, Laederach-Hofmann K, Wieselthaler G, with left ventricular assist devices as destination ther- Roethy W, Wolner E (2010) Mechanical circulatory apy. Curr Heart Fail Rep 8:212–218 477 V Adverse Events Management Contents Chapter 46 Ischemic and Hemorrhagic Stroke – 479 Rachel A. Pieri Chapter 49 Infectious Complications – 513 Ezin Deniz, Christina Feldmann, Jan D. Meyer and Ivan Netuka Chapter 51 Concomitant Noncardiac Surgery During Mechanical Circulatory Support: Management of Therapy – 545 Rachel A. Patients practitioners working with the mechanical circu- on mechanical circulatory support, as with the latory support patient population must be in tune general population, may be aficted by either with the unique risk profle of patients in the vigi- embolic or hemorrhagic strokes. In the postim- lant attempt to prevent patients from experienc- plantation period, diferent circumstances may ing this devastating complication. Owing to the fact that the destination tory of stroke, and hypertension; and secondary therapy population is more sick and thus less likely complications that may develop in relation to to be a candidate for future transplantation, one implantation and the need for and use of antico- might expect this group to not only sufer from agulation in the postsurgical period all have the more advanced heart failure but also more exten- potential to increase an individual’s proclivity sive comorbidities. Tis has of the medical team contributing to and advanc- been recorded in the literature as such. When ing the care of the patient on mechanical circula- overall stroke incidence is investigated between tory support must be ever aware of the incidence these two cohorts, it is demonstrated that this of stroke, its efects on the long-term patient care is the case. Te propensity for women thrombus formation at cannulation or migrated to sufer stroke events in signifcantly greater num- cannula sites as potential causes for thrombus for- bers than men warrants a greater investigation to mation [16]. Each available device would carry its own subtype over another and may potentially be use- set of thrombogenic risk due to the nature of ful in understanding the mechanisms behind the materials used in its manufacture. Several emulation methods and models are being design to test and evaluate the throm- Some studies have found a relatively balanced bogenic potential and thromboresistance of percentage of ischemic and hemorrhagic strokes devices [18–20]. Tese diferences in stroke etiology may refect qualitative assessment of one device in compari- the individual patient cohort and preoperative son to its peers, and it may therefore be impos- risk factors. Each patient and their individual risk sible to isolate the intrinsic thrombogenic efect profles should be considered preoperatively in and stroke risk profle of any one particular device order to gear management strategy toward their in a quantitative, predictive manner. Te incidence of embolic strokes has many pos- In demonstrating a better outcome for later- sible causes. Morgan occurs is likely to have a signifcant infuence on themes surrounding the postulations as to the patient recovery and long-term prognosis rather mechanism of hemorrhagic stroke development than only the device fow itself. With no dif- pump structure; these forces can cause the platelet ference in patient anticoagulation profles, 59. Reduced von Willebrand factor leads analysis and gives support to the increased inci- to pathologic bleeding and may play a role in the dence of right-sided strokes and its correlation development of hemorrhagic strokes. In the frst category, and Morbidity hemorrhagic transformation from angiogenesis and reperfusion at the site of a previous infarct Adverse neurological events can have a signifcant is attributed to the migration of prior emboli efect on patient mortality, future ability to receive fragments [22]. Te second hypothesis relates to cardiac transplant, and prolong the patient recov- the advent of rupture and bleeding from blood- ery period. Hence, the main cant diferences in mortality related to ischemic 483 46 Ischemic and Hemorrhagic Stroke versus hemorrhagic stroke , the mortality rate if other risk factors for embolic stroke are absent. Te cal circulatory support can experience signifcant ability to observe nuances in patients’ individual quality of life changes or rehabilitation setbacks. Tus, apy in order to decrease the risks of subsequent one would naturally expect that diabetic patients thromboembolic events and their complications. It is pos- stroke may refect a patient’s proclivity toward sible that the increased stroke risk in diabetics developing one type of stroke versus another. As opposed to the complete clamping, par- lowered for patients placed on antihypertensives, tial clamping refrains from compressing the pos- and risk is not dependent on the number of medi- terior aorta. It is possible, therefore, that complete cations required to control blood pressure [23–26]. Tis incidence increases to 45% when dent risk factor for postimplantation stroke. Te median time such an event can therefore put the patient at an to hemorrhagic stroke was 12 days compared to increase for stroke. Tis points to the importance 49 days for ischemic strokes, while infection was of properly anticoagulating the patient while keep- not associated with higher risk of ischemic stroke ing in mind their additional risk factors for stroke. Eur ences in the etiology of stroke, and 60% of strokes J Cardiothorac Surg 42(4):612–620. Ischemic and hemorrhagic supported with a continuous-fow left ventricular strokes have unique pathogenic mechanisms. Aspects unique to the care of patients device implantation: outcomes in the continuous-fow with assist devices such as the inherent device era.
Sun F buy levothroid 200 mcg without prescription thyroid symptoms in kittens, Zhang Y levothroid 50 mcg online qigong thyroid gland, Tian D et al (2011) Responses after one dose of a monovalent influenza A (H1N1) 2009 inactivated vaccine in Chinese population—a practical observation levothroid 100mcg low price thyroid cancer incidence. Yang G levothroid 200 mcg free shipping thyroid nodules hypothyroidism, Zhou B, Wang J et al (2008) Expression of recombinant Clostridium difficile toxin A and B in Bacillus megaterium. McGuinness R (2007) Impedance-based cellular assay technologies: recent advances, future promise. Fang Y (2006) Label-free cell-based assays with optical biosensors in drug discovery. Planche T, Aghaizu A, Holliman R et al (2008) Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. He X, Wang J, Steele J et al (2009) An ultrasensitive rapid immunocytotoxicity assay for detecting Clostridium difficile toxins. Slanina H, Konig A, Claus H, Frosch M, Schubert-Unkmeir A (2011) Real-time impedance analysis of host cell response to meningococcal infection. Am J Trop Med Hyg 78:434–441 8 Functional Assessment of Microbial and Viral Infections… 175 48. Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S (2002) Antigen presentation and T cell stimulation by dendritic cells. Am J Trop Med Hyg 81:163–170 Chapter 9 Cellular Fatty Acid-Based Microbial Identi fi cation and Antimicrobial Susceptibility Testing Nicole Parrish and Stefan Riedel Introduction Bacteria produce a wide array of complex lipids and fatty acids. Both fatty acids and complex lipids can vary in chain length, number and position of functional groups, and number and position of double bonds. The variability of fatty acid structure in bacteria has led to the characterization of over 300 bacterial fatty acids and related compounds. These fatty acids and related compounds range from relatively polar lipids found in bacterial membranes to more complex lipids found in lipooligosaccharides and lipopolysaccharides. Other fatty acids are components of highly specialized lipids, such as the mycolic acids, found in Mycobacteria, Nocardia, and related genera. Specialized methods have been developed for detailed analysis of fatty acids and related lipids. These methods have aided efforts in bacterial classification yielding both qualitative and quantitative analysis of specific fatty acids and their constituent components. Such methods have provided the basis for bacterial identification and taxonomic classification and continue to be used by many laboratories as an inex- pensive and rapid screening tool or as an ancillary test to other standard bacterial identification methods. So specific are the fatty acids contained within some of the larger lipids that the presence or absence of a particular chemical species can be indicative of a gram-negative or gram-positive organism. The vast majority of bacteria synthesize fatty acids with chain lengths ranging from 10 to 19 carbons in length, with hexadecanoic acid being the predominant type. The fatty acids of gram-negative bacteria tend to have a higher proportion of straight-chain, saturated and monounsaturated cellular fatty acids comprising even numbers of car- bon atoms. Other organisms have both straight-chain and unsaturated cellular fatty acids (Streptococci and coryneforms). In contrast, eukaryotic cells of humans and fungi typically lack the branched-chain and cyclopropane-containing fatty acids found in bacteria [5 ]. Although various procedures have been utilized over time, the most commonly used procedure involves a four-step process in sample preparation. Initially, cells are harvested (approximately 20 mg wet weight) off specific solid media from an area of the plate which represents log phase growth. Once harvested, fatty acids are saponified using a sodium hydroxide–methanol solution for 30 min at 100 °C. The saponification breaks cova- lently linked fatty acids from cellular lipids and the application of heat accelerates the process. The free fatty acids are then methylated using hydrochloric acid and methanol at 80 °C for 10 min followed by extraction into an organic solution of hexane and methyl t-butyl ether for 10 min. Fatty acids ranging from 9 to 20 carbons (9:0 to 20:0) are identified and quantified. Each fatty acid profile is then compared to a library database containing greater than 100,000 entries from strain collections obtained from around the world [ 10]. This is an important consideration since geographic bias is possible given that microbes occupy a wide variety of environmental conditions. In addition, for each species or subspecies, approximately 20 or more strains of each species tested were included in the analysis to allow for strain-to-strain variation [10, 11]. The particular fatty acid profile of an unknown organism is compared with the mean fatty acid composition of the strains used to create the library entry or entries listed as its match. The resulting similarity index represents the relative distance from the popu- lation mean for a given species. Currently available libraries include a large number of bacterial genera and species including aerobic bacteria (192 genera; >700 spe- cies), anaerobic bacteria (92 genera; >500 species), Mycobacteria (>31 species), and bacterial agents of bioterrorism (five genera; six species) [10]. In addition, a rapid sample preparation method is also available designed to identify environmental aerobes and yeast in less than 15 min from pure culture [10 ]. Library Expansion and Fatty Acid Polymorphisms As our ability to recover and identify new organisms or subspecies or strain varia- tions within the same genus increases, it will become extremely important that stan- dardized culture conditions are being used to routinely expand current library entries and databases now in use for identification. It is important to recognize that discrep- ancies in identification may occur as a result of variation in the similarity index, and may also reflect poorly defined library entries (i. Discrepancies in identification may also occur due to organisms which are very closely related biochemically and genetically. However, the fatty acid composition of all strains within a species is not neces- sarily homogeneous. However, when ratios for specific fatty acids were examined more closely (12:0/16:0 and 14:0/16:0) it was determined that the genus Yersinia could be separated into three distinct clusters, the last of which contained Y. Findings such as these indicate that just like genetic poly- morphisms, fatty acid polymorphisms may occur within each genus and species and also between strains. The presence of such polymorphisms may lead to difficulties in interpretation if they are not represented in the currently used database. Such issues can be overcome by inclusion of additional strains of a given species which may broaden the fatty acid profile and provide more precise separation from other taxonomically similar organisms. Identification of Agents of Bioterrorism and Other Select Agents The recent threat of bioterrorism has resulted in development of technologies which can rapidly detect and identify select bacterial agents. Separation of organisms suitable for biowarfare and bioterrorism from related nonpathogenic species within the same genus is based upon unique fatty acid profiles between the two. It is very dif fi cult, for example, to differentiate the two closely related Yersinia species, Y. The fact that these two organ- isms are genetically very close also poses difficulties for the use of molecular test methods. This necessarily exposes laboratory personnel to potentially dangerous pathogens; thus proper training and handling of the organism(s) are of paramount importance. Mycolic Acid Analysis for Identi fi cation of Mycobacteria Mycobacteria produce unique fatty acids known as mycolic acids.
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It is designed to increase the Te maxillary sinus is lined with ciliated columnar epithe- vertical posterior maxillary alveolar dimension for placement lial cells levothroid 200 mcg lowest price thyroid gland meaning in urdu, which clear secretions toward the ostia generic 50 mcg levothroid with mastercard thyroid symptoms body aches. Te sinus lift procedure in 1976 at an implant meeting in Bir- medial wall of the sinus has an opening (ostia) that connects mingham buy 50 mcg levothroid with mastercard thyroid body type diet, Alabama order levothroid 200 mcg visa thyroid cancer hgtv. Te opening is in the hiatus semilu- became the frst to publish this surgical technique, followed naris, which drains into the middle meatus of the nasal cavity. Tese hiatus ranges from approximately 18 to 35 mm (mean, procedures are routinely performed on an outpatient basis, 25. With the evolution of predictable sinus lift methods, this Te maxillary sinus receives its blood supply from branches technique has become one of the primary surgical options of the internal maxillary artery, including the infraorbital, 12 allowing placement of dental implants in the posterior sphenopalatine, greater palatine, and alveolar arteries. Te principles of the sinus lift procedure are simple; however, a number of anatomic variations and techniques should be considered to achieve reliable outcomes. Indications for the Use of the Procedure Te apex of the sinus extends to the zygomatic process of the maxilla. Te foor of the maxillary sinus is approximately Te primary indication for the sinus lift procedure is pneu- 5 1 cm below the nasal foor in dentate adults. Te base of the matization of the maxillary sinus, which prevents the place- pyramid contributes to the lateral wall of the nasal cavity. Poor bone three-sloped walls of the pyramid are formed by the orbital quality that prevents adequate initial stability during implant foor and the anterior and lateral walls of the maxillary sinus. Dental extraction in the Te sinuses are theorized to reduce the weight of the skull, posterior maxilla appears to be partly responsible for pneu- provide resonant function, regulate the inhaled air humidity, matization in elderly patients. Te approximate dimensions of curved sinus foor conforms to the conical root apices of 5 the maxillary sinus in adult males are 21 to 29 mm in width, posterior maxillary teeth. Te main location of 11,17 sinus pneumatization occurred in an inferior direction after the septa was the region of the frst and second molars. When septa were identifed in one maxillary sinus, there was Preoperative planning is essential for successful manage- a 66% to 70% chance of the same sinus confguration on the 17,21 ment of the patient. Tis may make it difcult to perform a cal exam, in addition to preoperative radiologic investigation, sinus lift. If the sinus is large, the walls may be thin, and the converse also is often true. Small sinuses also may have 22 Limitations and Contraindications thick osseous lamellae. Questions of lateral sinus walls were thin, and 48% of maxillary sinuses designed to elicit risks for sinus obstruction should be asked had septa. Te mean thickness of the maxillary sinus ranged 22 24 22 as part of the preoperative assessment. Tese sinusitis (the former defned as a sinus infection lasting more results also suggest that lateral pneumatization is not age than 4 weeks and the latter as at least four episodes of acute related, contrary to the fndings of Lee et al. Te schneiderian particularly systemic diseases and pathologies that interfere membrane should be kept intact to contain the graft material with mucosal composition or ciliary movements (e. Clinical evaluation of the or secondary immunodefciencies, cystic fbrosis, Kartagener’s lateral sinus wall can provide valuable information during and Mounier-Kuhn’s syndromes, dehydration, ciliostatic surgery. If the lateral sinus wall is thin and looks grayish blue, drugs, peripheral hypereosinophilia, asthma, chronic pulmo- the outline of the sinus can be determined easily. The remainder of the incision to the tuberosity region, with a releasing incision posterior to the is dictated by the presence or absence of teeth. This trapezoidal fap, which is designed to be broad is edentulous and bilateral sinus lifts are planned, the crestal based, allows minimal disturbance of the blood supply, suffcient incision extends anteriorly, crossing the midline to the opposite coverage of the surgical wound, and adequate access for the side. It The osteotomy of the lateral sinus wall is created as a curved is prepared initially with a 3 mm–diameter cutting round bur or window, following the foor and anterior wall of the maxillary piezoelectric handpiece with a round tip. The posterior aspect of the osteotomy extends to the molar sinus lift window should be wide enough to easily accommodate region, turning vertically. The superior aspect of the osteotomy the sinus lift instruments (Figure 22-1, B and C). After initial elevation of the membrane the membrane while bringing the trapdoor into a horizontal posi- along the inferior, anterior, and posterior aspects, the bone tion (Figure 22-1, D and E). B, Creation of an osteotomy along the lateral aspect of the right maxillary sinus wall. D, Te sinus membrane has been elevated, and the lateral window has been in-fractured. Alternatively, biologics, such as The space beneath this lifted door and sinus mucosa can be flled bone morphogenic proteins, have also been successful (Figure with graft material. G, Particulate allogeneic bone graft has been placed along the sinus foor of the right maxillary sinus. The primary stability The decision whether to insert the implant simultaneously with of a dental implant might not be adequate if the bone height is the sinus lift procedure or in a second-stage procedure depends less than 4 mm. A dental implant can be inserted in the second 30-33 on the ability to achieve primary stability of the implant. The width bone quantity and quality are essential for dental implant place- of the alveolar crest is also important for the longevity and stabil- ment. If the alveolar width is less than 5 mm, pneumatization of the maxillary sinus often compromise the ability augmentation should be considered or a ridge split technique may 34 to place dental implants. H Implant placement J I Figure 22-1, cont’d H, Panoramic radiograph approximately 6 months after removal of tooth #2 and 8 months after the sinus lift. Primary implant stability is a requirement for performed if the alveolar crest width is sufcient and the this technique. The depth of the osteotomy is 2 mm below the maxillary sinus foor (Figure 22-2, B). Tis can also be done with allogeneic bone by placing the graft mate- rial in the osteotomy and tapping it upward to begin to elevate the sinus foor. D, Te implant is placed and used to elevate the sinus foor about 3 to 5 mm to help tent the sinus membrane superiorly. Te bone graft is then applied nique involves creating a ridge-split osteotomy, after which internally, with or without immediate implant placement the principles and sequence of the transalveolar approach are (Figure 22-3). Ridge splitters, expanders, or chisels are inserted A B Figure 22-3 A, Crestal incision with minimal elevation of the fap. B, A spatula osteotome is used to deepen the osteotomy but staying about 2 mm below the maxillary sinus foor. However, tion of any graft material, appeared to have little infuence on this technique is difcult to manage if the sinus membrane the histologic characteristics of the sinus membrane. Te sinus membrane should be carefully Complications elevated and released from the sinus walls around the perfo- ration. Te Maxillary sinus foor elevation with or without graft material biodegradable membrane can be shaped and contoured to has proven to be a reliable method that enables the insertion cover and reinforce the membrane defect. Graft material can of endosseous implants in patients with a severely resorbed be simultaneously placed and retained in this sinus lift repair. Te complications of maxillary sinus foor elevation When the perforation is very large in an unfavorable area, procedures include perforation of the sinus membrane, loss delayed sinus lift should be considered. Reentry sinus lift of implants, local wound dehiscence, intraoperative hemor- rhage, graft infection, postoperative maxillary sinusitis, and 23,45,46 loss of graft.
Other arteries showed interposition as in most other types of injury with a membranoprolifera- mild intimal inflammation generic levothroid 200mcg mastercard thyroid releasing hormone. Another characteristic finding in chronic antibody-mediated rejection affects the peritubular capillary basement membranes buy levothroid 50mcg with visa thyroid nodules graves disease. Notice that in this image cheap 200mcg levothroid fast delivery thyroid gland boosters, the capillary basement membrane has six to eight distinct layers cheap 100mcg levothroid visa thyroid cancer quotes. The lumen contains a multi- layered platelet, which is somewhat analogous to the basement mem- brane duplication in chronic transplant glomerulopathy. This alteration likely results from repeated episodes of endothelial cell injury and repair, a postulate supported by the presence of a positive C4d stain 188 5 Renal Transplantation 5. Patients present with renal failure and decreased urine output, as well as graft tenderness in severe cases. It may coexist with C4d-associated acute humoral rejection, chronic changes, and even calcineurin inhibitor effects. The infiltrating cells expand the interstitium In type I T-cell–mediated rejection, mononuclear cell inter- and infiltrate the tubules, a process known as tubulitis. Distal tubules are stitial infiltrates with interstitial edema are the prototypic preferentially affected. In this case, there is extensive inflammation but only moderate tubulitis (t2) fi ndings. The interstitial in fl ammation may be associated with eosinophils and plasma cells. The hallmark of acute cellular rejection is infiltration of tubular epithelium by mononuclear cells, known as tubulitis. Acute tubular epithelial cell injury is observed, and the tubu- lar basement membrane may be disrupted. Glomerular inflammation, known as acute transplant glomerulitis, also may be present; however, this finding does not affect the Banff score. Type I T-cell–mediated rejection may coexist with acute humoral rejection, but inflammation of arteries and arterioles is absent. There is endothelial cell enlargement with subendothelial mononuclear cells, known as endovasculitis or endotheliitis. The tubule cell nuclei are large and vesicular, whereas the lymphocyte nuclei are smaller and dark. In addition, there is interstitial ence of tubulitis by defining the limits of the tubular basement mem- in fl ammation and prominent interstitial edema brane and differentially staining the tubule cells (pale and large) and the nuclei of lymphocytes (small and dark). This case shows severe rejection-associated reactive acute transplant glomerulitis. However, some both negative of the nuclei represent endothelial cells, contributing to the impression. The lower threshold for this diagnosis has not been established, and its treatment is as for a pure tubulointerstitial pattern of rejection Fig. Acute cellular rejection may involve glomeruli, usually in association with interstitial rejection. This image example of acute vascular rejection shows nearly circumferential inti- shows a mixed acute and chronic transplant glomerulopathy. In addi- Acute vascular rejection is characterized by endotheliitis affecting arte- tion to endotheliitis, thrombosis also may develop in acute vascular rioles and small arteries. In this example, subendothelial and luminal thrombosis is mononuclear cells are seen beneath the endothelium on the right. There also are chronic Enlarged reactive endothelial cells also are present changes with mild intimal fibrosis and multiple intimal foam cells 192 5 Renal Transplantation 5. There is marked intimal inflammation consisting predominately of T cells, and fibrointimal thicken- ing of arteries. Within the thickened intima, smooth muscle proliferation may occur, creating a neo- media. In contrast to hypertension-associated arterial disease, duplication and fragmentation of the internal elastic lamina do not occur. This example of chronic vascular rejection shows severe fi brointimal thickening with a distinct intimal–medial interface 5. The consequences of the severe arterial occlusive disease of chronic rejection is progressive Fig. In addition to fibrointimal thickening, arteries affected by demonstrated in this image. Plasma cells often are more prominent at chronic vascular rejection also may form a neomedia, a band of smooth this stage of rejection. In biopsy material, when no arterial or glomeru- muscle cells clearly located within the thickened intima. Also note the lar lesions of chronic rejection are evident, the terminology used is mild intimal inflammation with foam cells to the right. There is intense, tubular atrophy and interstitial fibrosis, no evidence of specific etiology diffuse cellular rejection throughout the cortex (previously referred to as chronic allograft nephropathy) Fig. Acute and chronic vascular rejection may affect chronic rejection, immunosuppression is stopped. Both types may be encountered in biopsies of older severe unchecked cellular and vascular rejection that may be associated allografts. This is a ubiquitous finding in chronically rejected allografts with infarcts leading to flank pain and systemic symptoms, prompting once immunosuppression has been discontinued. The allograph nephrectomy sample shown here allograph nephrectomy for symptomatic chronic rejection shows a is from a patient who had severe arterial occlusive disease with infarcts; small artery with fibrointimal thickening, as well as marked endothelii- one of the acute infarcts is visible in the image. It is characterized by a tis and mural in fl ammation wedge-shaped area of coagulation necrosis with a rim of hemorrhage 194 5 Renal Transplantation 5. A com- The latter is nonspecific in appearance and is not mon finding in cases of nephrotoxicity is no morphologic illustrated. The renal injury is mediated by arteriolar vaso- Calcineurin inhibitor toxicity includes: constriction that reduces the glomerular filtration rate, • Thrombotic microangiopathy resulting in azotemia. Lowering of the dose often leads • Hyaline arteriopathy quickly to improvement in renal function. The acute mor- • Isometric tubular vacuolization phologic lesions of calcineurin inhibitor toxicity are a • Interstitial (striped) fi brosis Fig. In contrast to hypertension and diabetes, in which the hyaline accumulation is subendothelial, in this lesion there are rounded accumulations of hyaline material preferen- tially located on the outer aspect of the arteriole. Their rounded nature reflects replacement of individual smooth muscle cells that have under- gone necrosis. Isometric tubular vacuolization is particularly well demonstrated the renal medulla. This case showed severe transmural hyaline arteri- with Masson trichrome stain opathy affecting the arteriolar vasa recta of the outer medulla Fig.
