By N. Ortega. Case Western Reserve University.
Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury generic kamagra oral jelly 100 mg on-line erectile dysfunction treatment bay area. Antifibrinolytic agents make alpha1- and beta2- microglobulinuria poor markers of post cardiac surgery renal dysfunction buy kamagra oral jelly visa outcome erectile dysfunction without treatment. Hyponatremia: A prospective analysis of its epidemiology and the pathogenetic role of vasopressin order 100mg kamagra oral jelly erectile dysfunction doctors in massachusetts. Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. Hungry bone syndrome: Still a challenge in the post-operative management of primary hyperparathyroidism: A systematic review of the literature. Hypophosphatemia: An evidence-based approach to its clinical consequences and management. Impact of acute kidney injury on distant organ function: Recent findings and potential therapeutic targets. Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: A population-based study. Acute renal failure in critically ill patients: A multinational, multicenter study. Prevention of radiocontrast nephropathy with N- acetylcysteine in patients with chronic kidney disease: A meta-analysis of randomized, controlled trials. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Acute kidney injury and death associated with renin angiotensin system blockade in cardiothoracic surgery: A meta-analysis of observational studies. Council on the Kidney in Cardiovascular Disease, the Council for High Blood Pressure Research of the American Heart Association. Renal considerations in angiotensin converting enzyme inhibitor therapy: A statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Nephrotoxicity in the elderly due to co- prescription of angiotensin converting enzyme inhibitors and nonsteroidal anti- inflammatory drugs. Does the combination of aprotinin and angiotensin-converting enzyme inhibitor cause renal failure after cardiac surgery? Acute renal failure in patients undergoing cardiothoracic surgery in a community hospital. The relationship of loop diuretics with acute kidney injury and mortality after cardiac surgery. Relation between the interval from coronary angiography to selective off-pump coronary artery bypass grafting and postoperative acute kidney injury. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Preoperative statin therapy is associated with lower requirement of renal replacement therapy in patients undergoing cardiac surgery: A meta-analysis of observational studies. Contrast-induced nephropathy may constitute a marker of underlying limited renal reserve for cardiac surgical procedures? Reversible renal vasoconstriction in a patient with acute renal failure after exercise. Dose-related biochemical markers of renal injury after sevoflurane versus desflurane anesthesia in volunteers. Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients with stable renal insufficiency. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. Clinical review: Volume of fluid resuscitation and the incidence of acute kidney injury: A systematic review. Human kidney methoxyflurane and sevoflurane metabolism: Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity. Inorganic fluoride nephrotoxicity: Prolonged enflurane and halothane anesthesia in volunteers. Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation. Plasma protein binding of etomidate in patients with renal failure or hepatic cirrhosis. Pharmacokinetics of propofol and haemodynamic changes during induction of anaesthesia in uraemic patients. The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment. Effects of renal insufficiency on the pharmacokinetics and pharmacodynamics of opioid analgesics. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children. Postoperative respiratory depression and elevated sufentanil levels in a patient with chronic renal failure. Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide. Pharmacokinetics of mivacurium in normal 3596 patients and in those with hepatic or renal failure. Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure. Atracurium, cisatracurium, vecuronium and rocuronium in patients with renal failure. The pharmacodynamics and pharmacokinetics of vecuronium in patients anesthetized with isoflurane with normal renal function or with renal failure. Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure. Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure. Effect of renal function on neuromuscular block induced by continuous infusion of mivacurium. Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: A pharmacokinetic study. Acute mountain sickness and acetazolamide: Clinical efficacy and effect on ventilation. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. What we can learn from the selective manipulation of dopaminergic receptors about the pathogenesis and treatment of hypertension? Trends in acute renal failure associated with coronary artery bypass graft surgery in the United States.
It could be less than one-half or purchase line kamagra oral jelly erectile dysfunction medicine online, as is likelier in practice order 100 mg kamagra oral jelly free shipping erectile dysfunction drugs otc, more than one-half discount kamagra oral jelly 100mg erectile dysfunction 30s. Therefore, simulating both the specific infusion context as well as the required percentage decrease from the target concentration should be done to get the best estimate of when a drug’s effect will reach the clinically desired end point. Figure 11-18 The context-sensitive 25%, 50%, and 75% plasma decrement times for fentanyl, alfentanil, sufentanil, and remifentanil. Although a 50% decrease in plasma concentration is an appealing and comprehensible parameter, larger or smaller decreases in plasma concentrations may be required for recovery from the drug. Simulations show that the times for different percent decreases in plasma concentration are not linear. In addition, if the concentration of interest is the effect site concentration rather 710 than the plasma concentration, simulations can be performed to calculate the context-sensitive effect site decrement time. Finally, if a constant plasma or effect site concentration is not maintained throughout the delivery of the drug (which is typically the case with manual bolus and infusion schemes and also with varying drug requirements depending on surgical stimulation, etc. If precise drug administration data are known, it is possible to compute the context-sensitive decrement time for the individual situation or context. Soft Pharmacology and Anesthesiology Accumulation of drug in well perfused but inactive tissue beds (i. When the arterial concentration of drug is less than the tissue concentration of drug in any of these tissue depots, the drug redistributes from the tissue back into the plasma, thereby slowing the rate of decline of the plasma concentration. One strategy that has been used to limit tissue uptake of drug is to design active compounds that are rapidly metabolized by plasma and/or tissue enzymes into inactive metabolites—so-called soft drugs. However, the preclinical data have resulted in selection of an etomidate analog that has context insensitive decrement times as well as limited adrenal suppression. However, in the operating room, once the anesthetic has commenced, without the help of a computer, software, and possibly an assistant, it is laborious and difficult to make any calculations to determine how to adjust the infusion or how to bolus (or stop the infusion) to increase or decrease the target plasma concentration. The blue line represents the predicted plasma propofol concentration of 5 μg/mL, which in theory is attained at time t = 0 and is then maintained by a variable rate infusion. The red line is the predicted effect site concentration under the conditions of a constant pseudo–steady-state plasma concentration. Note that 95% of the target concentration is reached in the effect site at approximately 4 minutes. The success of this approach is influenced by the extent to which the drug pharmacokinetic and pharmacodynamic parameters programmed into the computer match those of the particular patient at hand. For a computer-control pump to produce and maintain a plasma drug concentration it must first administer a dose equal to the product of the central compartment, V , and the target concentration (1 Fig. Then for each moment after that, the amount of drug to be administered into the central compartment to maintain the target concentration is equal to drug eliminated from the central compartment plus drug distributed from the central compartment to peripheral compartments minus drug returning to the central compartment from peripheral compartments. The software keeps track of the estimated drug in each compartment over time and applies the rate constants for intercompartmental drug transfer from the pharmacokinetic model to these amounts to determine drug movement at any given time. It then matches the estimated concentrations to the target concentration at any time to determine the amount of drug that should be infused. The software can also predict future concentrations, usually with the assumption that the infusion will be stopped so that emergence from anesthesia or the dissipation of drug effect will occur optimally according to the context-sensitive decrement time. The orange line represents the predicted plasma propofol concentration (Cp) that results from a bolus dose, given at time t = 0, that is predicted to purposely overshoot the plasma propofol concentration target until time t = Tmax (1. At Tmax pseudo-equilibration between the effect site and the plasma occurs and both concentrations are then predicted to be the same until the target is changed. Note that the effect site attains the target in less than half the time with effect site targeting compared to the plasma concentration targeting seen in Figure 11-20. By adding the kinetics of the effect site it is possible to target effect site concentrations as would be in keeping with the principle of working as closely to the relevant concentration–effect relationship as possible. A dose scheme that targets concentrations in a compartment remote from the central compartment (i. In principle, targeting the effect site necessitates producing an overshoot in plasma drug concentrations during induction and for subsequent target increases. This is similar in concept to overpressurizing inhaled anesthetic concentrations to achieve a targeted end-tidal concentration. However, unlike the inspiratory limb of an anesthesia circuit, the plasma compartment seems to be closely linked to cardiovascular effects, and large overshoots in plasma drug concentration may produce unwanted side effects. Thus, incremental adjustments in the target should result in incremental and stable new concentrations in the patient as long as the incremental adjustments are not too frequent. Figure 11-22 The influence of the misspecification of each of the components of the traditional three compartment pharmacokinetic models on the prolonged discrepancy (overshoot) between predicted and targeted concentrations with target-controlled infusions. The error resulting from elimination clearance was negligible and therefore not illustrated. Other software systems were developed in North America by groups at Stanford University and Duke University. This greatly increased both anesthesiologists’ interest in this mode of delivery and their understanding of the concentration–effect relationships for hypnotics and opioids. Stanpump currently provides pharmacokinetic parameters for 19 different drugs, but has the ability to accept any kinetic model for any drug provided by the user. This delay, or hysteresis, is presumed to be a result of transfer of drug between the plasma compartment, V , and an effect compartment, V , as well as the time requiredC e for a cellular response. By simultaneously modeling the plasma drug concentration versus time data (pharmacokinetics) and the measured drug effect (pharmacodynamics), an estimate of the drug transfer rate constant, k , between plasma and the putative effect site can be estimated. Likewise, it is not valid to compare estimates of k among studies of the same drug or across different drugs and, therefore,e0 one should not be surprised that reported values for k for the same druge0 vary markedly among studies. The model-independent parameter that characterizes the delay between the plasma and effect site is the time to maximal effect, or T. The concept of a transportable, model-independent parameter that characterizes the kinetics of the effect site is important for robust effect site– targeted, computer-controlled infusions. This is because there are many more pharmacokinetic studies characterizing a wider variety of patient types and groups in the literature than there are complete pharmacokinetic– pharmacodynamic studies. By making the generally valid assumption that interindividual differences are small in a drug’s rate of effect site equilibration, it is possible with a known Tmax to estimate effect site kinetics for a drug across a wide variety of patient groups where only the pharmacokinetics are known. It is possible to calculate a bolus dose that will attain the 717 estimated effect site concentration at Tmax without overshoot in the effect site. This is done by combining the concept of describing drug distribution as an expanding volume of distribution that starts at V and approaches V (theC β apparent volume of distribution during the elimination phase) over time with the concept of Tmax. In practical terms this bolus is given at time t = 0, after which the infusion stops until time t = Tmax. In the case of the propofol kinetics used to construct the isoconcentration nomogram in Figure 11-15, the pharmacokinetic– pharmacodynamic parameter set of Schnider et al. Thus the proper propofol bolus for a targeted effect site propofol concentration of 5 μg/mL is 109 mg. The computer- controlled infusion pump will deliver this dose as rapidly as possible and then begin a targeted infusion for 5 μg/mL at t = 1. Recirculatory pharmacokinetics and pharmacodynamics of rocuronium in patients: the influence of cardiac output. These kinetic events and the drug39 concentration versus time profile that results are important because the peak effect of rapidly acting drugs occurs during this temporal window.
Trichrome stain hightlights the rigid shape of a cast and often shows the intense bicolor staining pattern shown here generic kamagra oral jelly 100mg visa erectile dysfunction young cure. This case con- tained numerous small rectangular to rhomboid-shaped cheap kamagra oral jelly 100 mg without prescription best erectile dysfunction pills treatment, densely eosino- philic crystals within tubules buy kamagra oral jelly 100 mg free shipping candida causes erectile dysfunction. Although these crystals showed light chain restriction by immunoﬂuorescence, light chains in crystalline form may Fig. A cytokeratin stain nicely demonstrates that the be negative by routine immunoﬂuorescence. In this case, the casts stain strongly for kappa light chain whereas the lambda light chain stain was completely negative. This problem may be compounded because the crystals may not stain by immunoﬂuorescence. However, antigenic sites are more read- ily available to light chain antisera with pronase digestion. Ultrastructural identiﬁcation of the light chain crystals is easy because most of the tubules are affected. The intracellular crystals have a variety of shapes, mostly ranging from triangular to square with sharp crisp angles. This case of light chain crystal tubulopathy shows two proximal tubules in which all the cells are stuffed with tiny light chain crystals. This case shows subtle granular- ity to the proximal tubule cytoplasm, which is loaded with light chain crystals. In this disease, the crystals are located within inﬁltrating histiocytes rather than cells of the nephron. Like light chain crystal tubulopathy, the antigenicity of the crystals may be impaired in frozen tissue, necessitat- ing pronase digestion to demonstrate light chain restriction. This electron micrograph shows large histiocytes with intracellular vacuoles ﬁlled with light chain crystals Fig. Crystal-storing histiocytosis, like light chain crystal tubulopathy, may be very subtle on routine his- tologic stains. This case contains numerous interstitial histiocytes laden with light chain crystals. The histiocytic cells and their intracellular crystals are readily seen on review of toluidine blue stain of 1-mm sections for electron microscopy. In the living chain restriction is noted within the proximal tubule cyto- patient, the involvement may be subclinical or overt, with plasm where lysosomal granules are ﬁlled with a single light presentation in acute renal failure. More cases are the result of lambda light chains than marked renal enlargement; extrarenal disease also is usually kappa light chains. This biopsy specimen is from a patient with chronic lymphocytic leukemia who presented with unexplained acute renal failure. The neo- plastic inﬁltrate in lymphoproliferative-related diseases typically forms Fig 3. The light chain etiology of the injury was not uli, a distinctive ﬁ nding at low magni ﬁ cation apparent, and no other light chain lesion was present. However, on immunoﬂuorescence, the proximal tubules contained numerous cyto- plasmic lysosomal granules that stained only for lambda light chain. This renal biopsy was performed in a renal transplant patient for unexplained acute renal failure. The biopsy specimen shows a large cell B-cell lymphoma related to an Epstein-Barr infection. The lymphomatous inﬁltrate is extensive, again widely separating the renal tubules. The cytologic features in this case make the diagnosis straightforward 134 3 Tubulointerstitial Diseases 3. Calcium phosphate crystals, calcium oxalate crystals, and small med- ullary urate granulomas are common minor ﬁndings at autopsy and frequently occur in end-stage kidney disease. However, more widespread deposition of these crystals may represent serious exogenous or endogenous metabolic renal diseases. Furthermore, several drugs, such as antiviral agents, may precipitate within renal tubules, providing important evidence of an iatrogenic cause of renal failure. Crystals and pigments may be present in the following: • Acute phosphate nephropathy • Nephrocalcinosis • Randall’s plaque and nephrolithiasis Fig. This • Renal tubular oxalosis ﬁeld is from an autopsy kidney from a patient who died with dissemi- – Primary hyperoxalosis, types 1 and 2 nated lymphoma. The lymphoma extensively involved the kidney, – Secondary oxalosis, exogenous and endogenous resulting in massive bilateral involvement and renal failure. The patient died of urosepsis • Cystinosis – Infantile nephropathic cystinosis – Juvenile cystinosis (see Figs. The history is crucial to establishing the etiology because nephrocalcinosis resulting from other hypercalcemic or hyperphosphatemic causes have a similar appearance Fig. This is a bowel prepara- tion–associated example secondary to a phosphate-containing enema. There is widespread deposition of calcium phosphate crystals in the distal tubules and collecting ducts, and extending into the interstitium. Depending on the severity and timing of the biopsy, tubulointersti- tial scarring may be present, as in this case. In this case, the cause was chronic excessive use of phosphate-containing antacids. Interstitial ﬁ brosis is beginning to develop 136 3 Tubulointerstitial Diseases 3. The crystals may affect the tubular epithelium or decorate tubular and glomerular basement membranes and may be associated with nephrolithiasis. The biopsy specimen is from a renal transplant patient with severe chronic renal failure associated with secondary hyperpara- thyroidism prior to transplantation. The biopsy was performed because of renal failure that developed shortly after transplantation. The speci- men shows numerous tubules containing intraluminal calcium phos- phate crystals 3. It may be secondary to an exog- enous exposure (most common), such as ethylene glycol (antifreeze), methoxylﬂurane anesthesia, dioxane poison- ing, pyridoxine deﬁciency, or excessive vitamin C ingestion, or may have an endogenous origin, secondary to pancreatic insufﬁciency, gastrointestinal disease. Shown is a Randall plaque consisting of extensive interstitial calciﬁcation with formation of a microcalculus. If a patient ingests something that delivers a heavy oxalate load to the renal tubules, they will develop direct tubular injury associated with precipitation of oxalate-containing crystals. This image of chronic pyelonephritis with marked caliectasis also shows a staghorn calculus in situ. Although staghorn calculi commonly are associated with development of xan- thogranulomatous pyelonephritis, this does not occur in every case 138 3 Tubulointerstitial Diseases Fig.
Schirrmeier H best order kamagra oral jelly erectile dysfunction pumps side effects, Strebelow G purchase kamagra oral jelly overnight erectile dysfunction meds online, Depner K order cheap kamagra oral jelly online impotence specialist, Hoffmann B, Beer M (2004) Genetic and antigenic characterization of an atypical pestivirus isolate, a putative member of a novel pestivirus spe- cies. Muradrasoli S, Bálint A, Wahlgren J et al (2010) Prevalence and phylogenetic relationship of coronaviruses in wild birds from the Bering Strait Area (Beringia). Widén F, Sundqvist L, Matyi-Toth A et al (2011) Molecular epidemiology of hepatitis E virus in humans, pigs and wild boars in Sweden. Schlingemann J, Leijon M, Yacoub A et al (2010) Novel means of viral antigen identiﬁcation: improved detection of avian inﬂuenza viruses by proximity ligation. Xia H, Liu L, Nordengrahn A et al (2010) A microsphere-based immunoassay for rapid and sensitive detection of bovine viral diarrhoea virus antibodies. Liu L, Kampa J, Belák S, Baule C (2009) Virus recovery and full-length sequence analysis of atypical bovine pestivirus Th/04_KhonKaen. Liu L, Xia H, Wahlberg N, Belák S, Baule C (2009) Phylogeny, classiﬁcation and evolutionary insights into pestiviruses. Several sequencing platforms are available in the market and many more are being developed at various stages. Wang (*) Stanford Genome Technology Center, Department of Biochemistry , Stanford University , 855 S. The Illumina technology uses solid-phase ampliﬁcation to achieve clonal ampliﬁcation of sequencing templates on the surface of a glass slide where high- density forward and reverse primers are covalently attached. The Illumina HiSeq uses the cyclic reversible termination method, which comprises nucleotide incorporation, ﬂuorescence imaging, and cleavage steps. An imaging step follows each nucleotide incorporation step to capture the incorporated nucleotide at each cluster. The avail- ability of genotypic information on the viral drug targets allows doctors to adjust treatment regiment and to select a new potent drug combination after failure of antiviral therapy. Due to an associated replication or competitive disadvantage compared to the wild-type virus, newly emerged drug- resistant clone only represents a small proportion of the total viral load. Traditional Sanger sequencing is insensitive for minor alleles in a heterogeneous mixture of mutant and wild-type sequences with detection limit about 10 %. According to Poisson distribution, it needs to sequence about 300 clones to detect mutants at 1 % frequency with 95 % conﬁdence. The labor-intensive feature of this approach limits its usage in academic research settings. However, those sequencing reads are noisier with errors than those generated by Sanger sequencing. The Illumina sequencers have more substitution-type miscalls than indel-type miscalls, while the Roche/454 sequencers have more indel-type miscalls than substitution-type miscalls. The insertion/ deletion of one or two bases change the frame of coding region, which is lethal to viruses. Therefore, it is much easier to distinguish indel-type miscalls from actual indel mutations selected under the drug pressure than substitution miscalls from actual substitution mutations. Substitution miscalls resemble with actual mutations in many aspects and more sophisticated statistical procedures are needed to identify them. From those points, it appears that Roche/454 sequencer is more suitable for rare mutation detection than the Illumina one in the meantime. The following sections describe the data analysis procedures for detecting low-level viral drug- resistant mutants with the Roche/454 technique. Analyze Pyrosequencing Data for Detecting Low-Level Variants Map Pyrosequencing Reads onto Reference Sequences The output from the Roche/454 sequencing platform includes a quality score for every position in a read. Quality score in the Roche/454 sequencing platform is originally designed to measure the conﬁdence that the homopolymer length at that position is correct ; however, we found that the quality score of a position is also a good measurement of conﬁdence that the correct base is called at any position, as with a traditional Phred score. The Phred-equivalent quality value (q) is given by the log-transformed probability p of the base call being incorrect according to the equation q =−10×log10 p. Thus a base call with a quality value of q will have a −q/10 probability of 10 of being incorrect. To apply this algorithm, we transformed −q/10 the Phred scores into reliability weights W 1. As scores for bases in other regions are not lower than aver- age, weighting will not introduce artiﬁcial gaps in those regions. We found that the 37 Deep Sequencing: Technical Advances and Clinical Microbiology Applications 683 sizes of deletion (and insertion) errors follow the geometric distribution (data not shown) and the chance of missing more than one nucleotide due to sequencing errors is extremely low, so we did not weight gap-extension at reads (Ix in Fig. We did not weight mismatches to avoid mis-pairing due to low quality score of a particular base. The computational complexity of the Smith–Waterman algorithm is Onm where n is the length of a reference sequence and m is the length of a pyrosequencing read. Brieﬂy, the reference sequences are preprocessed to build a large lookup table of k-mers called “seeds” in the main memory for determining the positions of seeds in the long sequences efﬁciently. The query sequence (pyrosequencing read) is then scanned to associate individual seeds in the query with their positions in the reference, thereby listing candidate regions in the reference where the query and reference are likely similar. Filter Sequencing Artifacts Due to imperfection of sequencing technique, variants (mismatches between reads and consensus) of varying frequencies were observed at almost every position. The Poisson distribution is commonly encountered in biology in describing random occurrences of rare events in time when the events are independent. In other words, the occurrence of an event is assumed to have no effect on the probability of a second occurrence of the same event. The sequencing miscalls observed in pyrose- quencing reads are rare in comparison to the correct base-calling and approximately independent. Although miscalls within a few bases in the same reads might be related, miscalls far away and those in separate reads are absolutely independent. With this consideration, we chose the Poisson distribution to model the distribution of sequencing miscalls. The excess number of reads required to detect minor variants is a result of the Poisson model for handling potential sequencing errors. It is clear that more reads are needed to detect the variants of the same frequency in regions with higher error rate In order to use the Poisson distribution to model miscall, we ﬁrst need to estimate pyrosequencing error per base. As we described earlier, the pyrosequencing technique tends to make more miscalls in homopolymeric regions than non-homopolymeric regions. We classiﬁed miscalls into two categories, those in homopolymeric regions and those in non-homopolymeric regions, and computed the error rate for each category. With the availability of pyrosequencing error rates, we can compute the probability λ k of miscalls observed n times for each position with the formula p= ((e λ ) / k! To classify whether a minor variant with n occurrences in N reads is sequencing miscall or actual mutations in a viral genome, we calculated the probability that such a variant would occur n or more times if it were a sequencing miscall, using the fol- n−1 λ k lowing formula: p=−∑ e λ k. Using the Poisson model, we can also estimate the minimum coverage needed for the low-level variants of a particular frequency. The higher the error rate of a region, the higher the coverage needed to detect the variants of the same level of frequency.