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A reduction in nephron numbers often is related to prematurity trusted kamagra soft 100 mg, poor maternal health buy kamagra soft american express, and low birth weight 100mg kamagra soft with amex, and is physiologically important because it has been strongly correlated with risk of hypertension as an adult. The types of renal hypoplasia are: • Simple hypoplasia • Oligomeganephronic hypoplasia • Cortical hypoplasia • Segmental hypoplasia/Ask-Upmark kidney 2. However, if the renal mass is insufﬁcient to maintain proper homeostasis, with physical maturation nephron scle- rosis may ensue. The cortex is thin on the right side, and there is no column of Bertin between the two pyramids. Their combined weight and size, especially the kidney on the left, are less than half of normal. There was no histologic abnormality 24 2 Developmental Anomalies and Cystic Kidney Diseases 2. The daunting enlarged compared with nephrons in a patient of a similar name of this disorder describes its essential features. Patients present with nephrotic range proteinuria and kidneys are small with reduced numbers of renal lobes that develop renal failure at a young age. The enlarged nephrons may not be easily appreciated in a single photograph but require comparison with an image at similar magniﬁcation from a patient of comparable age. It also has more numerous glomerular capillary loops than normal, a feature that may be appreciated in this image. This is another example of oligome- ganephronia from a biopsy performed for proteinuria and renal insufﬁciency. This glomerulus is markedly enlarged and also appears to con- tain more numerous capillary loops than a normal glomerulus. Cortical hypoplasia refers to a reduction in nephron However, if a threshold for a diagnosis of cortical hypoplasia generations. Determination of nephron generations is best is set at a 50 % reduction in nephron generation—that is, accomplished with a nephrectomy specimen so that properly four to ﬁve generations in a properly oriented section—then oriented sections aligned along medullary rays are avail- the reliability of this assessment is reasonable. Cortical hypoplasia may be difﬁcult to rec- ognize histologically unless a well-oriented section shows the full corti- cal thickness along a medullary ray. In this image from a normal kidney, there are two medullary rays with three rows of nephrons aligned per- pendicular to the medullary ray tubules Fig. Notice that there are no medullary rays and that there is no evidence of nephron atrophy or metanephric dysgenesis Fig 2. Although the normal kidney should have 10–14 generations of nephrons, identifying more than 9 to 10 genera- tions in a well-oriented section is difﬁcult. Others, like the author, agree with reﬂux-related injury, but believe most cases are developmental in origin as a result of in utero reﬂux that damages the developing renal lobe. Segmental hypoplasia is deﬁned as a small kidney with a deep cortical groove(s) and dilatation of adjacent calyx. The cortex contains few tubules, with no or only rare glomeruli, little or no inﬂammation, and no evidence of metanephric dysgen- esis or nephron atrophy. The medulla is absent or ﬂattened with no loops of Henle and may contain a distinctive cellular Fig 2. This kidney is from a 17-year-old patient interstitial mesenchymal tissue not present in the normal renal with cortical hypoplasia. Extrarenal vascular anomalies occur in 40 % of cases of three nephron generations are present, and there is no atrophy or supporting a developmental abnormality. This example of segmental hypoplasia shows the circumferential deep cortical groove characteristic of segmen- tal hypoplasia. Only two to three nephron generations are present, and there is no atrophy or metanephric dysgenesis Fig. It is only 7 cm in length and contains a single circumferential deep cortical groove and dilated collecting system. In addition to the segmental hypoplastic focus, there was cortical hypoplasia with a reduc- tion in nephron generation to two to three generations in sections of oth- erwise normal cortex away from the groove, as shown in Fig. This developmental abnormality strengthens the postulate that segmental hypoplasia may have a developmental basis, at least in some cases Fig. There are multiple hyp- glomeruli are present to indicate an atrophic lesion oplastic foci, and the renal pelvis is signiﬁcantly dilated 28 2 Developmental Anomalies and Cystic Kidney Diseases Fig. It demonstrates the abrupt case shows the abrupt transition from normal cortex to the hypoplastic transition from normal cortex to the hypoplastic focus. The hypoplastic focus contains dilated veins, hypertrophied focus contains dilated veins, hypertrophied arteries, and several small arteries, infrequent small tubules, and mild inﬂammation. No tubular atrophy or glomerulosclerosis is atrophy, normal glomeruli, or glomerulosclerosis is present present Fig. This hypoplastic segment from the kidney of a 33-year-old woman shows how narrow the hypoplastic foci may be. Notice the normal cortex on both sides of the lesion and the characteristic abrupt transition. The hypoplastic focus contains thick- walled arteries, dilated veins, and no evidence of normal or sclerotic glomeruli 2. Potter syn- The most extreme form of reduced renal mass is renal agenesis drome results in neonatal death from pulmonary hypoplasia or complete absence of kidney and ureter. Renal agenesis because amniotic ﬂuid is required for proper lung develop- may be unilateral or bilateral. Neonates with Potter syndrome also have extrarenal radic or part of several malformation syndromes. Bilateral anomalies known as the Potter sequence or oligohydramnios agenesis is often referred to as Potter syndrome. The Potter sequence includes Potter facies, illus- kidneys are responsible for producing much of the amniotic trated later, and varus deformity of the lower extremities. Because the ureter contributes to the formation of the trigone musculature, the trigone will be abnormal. Male patients with unilat- eral agenesis often have no mesonephric duct–dependent structures and Fig. Louis: Mosby; 2008: Although the adrenals are present, both kidneys and ureters are absent. The renal disease varies greatly in sever- bilateral renal dysplasia, and distal complete urinary tract obstruction) ity. The most severe forms affecting neonates and infants lead will have Potter facies, which includes a broad beaked nose; bilateral epicanthic folds; low-set, often posteriorly rotated ears; and a recessed to death related to pulmonary hypoplasia. The impaired pul- mandible monary development is attributed to the massively enlarged kidneys that compromise the thoracic space. This is a useful histologic ﬁnding in older patients in whom the renal ﬁndings may not be diagnostic.
An increase in the proportion of robotic procedures was seen over the time period purchase kamagra soft 100 mg online, from 14 generic kamagra soft 100mg. Blood transfusion and prolonged hospital stay were less likely following robotic surgery order kamagra soft 100 mg with amex, and although intraoperative complications were higher, there was no difference in postoperative complications. Hospital charges were significantly lower in the open surgery population compared with robotic surgery patients. Robotic versus Laparoscopic Sacrocolpopexy Two randomized trials, and a retrospective cohort study comparing clinical outcomes and costs of robotic and laparoscopic sacrocolpopexy, have found robotic surgery costs to be higher than those of laparoscopic surgery [18,19,26]. Operating time was longer by 67 minutes, 14 minutes of which was robot docking time, in the robotic group. The differences in the two procedures, such as intracorporeal knot tying in the robotic group and extracorporeal in the laparoscopic group, may also have contributed to longer robotic operating time. It was postulated that differences in pain might be due to the greater number and size of ports in the robotic arm. This is a conservative estimate as robot acquisition and maintenance costs were not included in the analysis. The difference in costs was accounted for by the operating room costs since costs associated with hospital stay and postoperative care were similar. The other randomized trial of robotic and laparoscopic sacrocolpopexy reported surgical costs and costs associated with rehospitalization up to 6 weeks, as well as outcomes at 6 months . Costs were derived from applying a cost-to-charge ratio to the hospital charges rather than from accounting for individual costs of items used. Operating time was longer in the robotic group and short-term pain was greater in this group. It was felt that the increase in pain might be related to the operating time and the increased tension on the robotic ports due to a lack of tactile feedback from robotic surgery; i. Over 6 weeks, costs were higher for robotic surgery 1553 ($19,616 versus $11,573) but when purchase and maintenance costs were excluded, the cost difference decreased to only $1,000. They concluded that the higher costs were as a result of the robot purchase and maintenance, rather than surgical costs. Both of these studies stipulated that surgeons should have performed at least 10 of procedures of each type prior to starting the study. It is possible that the surgeons, who were experienced laparoscopists, were still at the start of the learning curve of robotic surgery after 10 cases. In the retrospective cohort study of 104 subjects, Tan-Kim also found that costs were higher for robotic surgery. Differences in surgical technique between the procedures may have contributed to this. Titanium tacks were used to fix the mesh to the sacrum in the laparoscopic group whereas suturing with intracorporeal knot tying was the method in the robotic group. Robot docking time accounted for only 9 of the 72 minutes difference in operating times. They also acknowledge that the study covered a period when some of their surgeons were at the start of their learning curve for the procedures. Cost Comparisons of Open, Laparoscopic, and Robotic Sacrocolpopexy A cost-minimization analysis by Judd  concluded that robotic was more expensive than laparoscopic or open sacrocolpopexy under baseline assumptions. They used two models; one based on current hospital ownership of a robotic system and one including the purchase and maintenance costs. Sensitivity analyses were performed to assess the effect of varying the parameters. They found robotic sacrocolpopexy to be the most expensive, with an incremental cost of $1155 over laparoscopic and $2716 over open sacrocolpopexy. Robotic and laparoscopic surgery costs only became equivalent when robotic operating time is reduced to 149 minutes, robotic disposable costs reduced to $2132, or laparoscopic disposable costs increased to $3413. The additional costs associated with the robot purchase model were between $581 and $1724 per procedure, depending on robotic throughput. The cost differences reflect higher disposable equipment costs and longer operating time. Despite these findings, the authors suggest that continued robotic innovation might lead to future cost savings in terms of reduced operating time and cheaper equipment. Operation times in this study were significantly greater than other referenced studies (418 minutes for open, 510 for laparoscopic, and 358 for robotic procedures). The estimated direct costs were higher for robotic surgery than open but not significantly different for robotic and laparoscopic approaches. It is not clear whether costs associated with robot purchase and maintenance are included in this analysis. Learning Curve of Laparoscopic and Robotic Sacrocolpopexy The learning process of laparoscopic sacrocolpopexy presents a challenge to most urogynecologists. Many of them have little experience of advanced laparoscopic surgery and are traditionally trained as predominantly vaginal surgeons. To become proficient in a new surgical technique, surgeons need a sufficient individual caseload. Even though vaginal prolapse is a common indication for surgery, vault prolapse is relatively uncommon. In order to assess the learning process, it is necessary to define an endpoint at which a surgeon is judged to be proficient. Assessment of the learning curve should include measures of quality and efficiency. Quality of surgery can be assessed by functional outcomes or by complication rates. Efficiency is usually assessed by measuring duration of surgery but may also include conversion to open surgery. A number of studies have attempted to quantify the learning curve of laparoscopic sacrocolpopexy. They focus on the number of cases required to reduce the operating time, largely due to low rates of reported complications associated with the procedure in the studies [28–30]. Operating time declined rapidly during the first 30 cases in the study reported by 1554 Claerhout et al. Dissection of the vault was the most time-consuming step; times comparable with the teacher (the control) were achieved after 31 cases. Duration of suturing fell within the range of the teacher after only 10 cases, but it should be noted that the participants had attended a 15 hour laparoscopic skills lab prior to commencement of the study. There was no learning curve associated with dissection and fixation to the sacral promontory. Two studies have found operative times to drop significantly after just 10 cases [32,33]. The learning curve of robotic hysterectomy has found to be significantly longer than these small series suggest. The extent to which this study can be extrapolated to robotic sacrocolpopexy is debatable and further studies of the learning process are required for this procedure.
For example purchase kamagra soft 100mg with amex, if the drug is 100% absorbed across the gut wall and the liver extracts 70% before it reaches the systemic circulation purchase cheap kamagra soft line, 30% of the dose finally reaches the bloodstream cheap kamagra soft american express. Therefore, we will consider the potential impact that changes in Qh, Fp, and Cli will have on the steady-state concentration of both total and free drug concentration. Remember, we will assume that Cl (totalt body clearance) equals Clh (hepatic clearance) and that steady-state free drug concentration is the major determinant of pharmacologic response. When trying to assess clinical implications, always consider the following: • route of administration (intravenous vs. In the following three examples, we apply the previously described hepatic extraction equation to several cases involving a specific disease state effect or drug interaction. Considerations • Theophylline (in this example) is administered via a constant intravenous infusion (K0). Because theophylline has a low extraction ratio and is not extensively bound to proteins, Clh = Fp × Cl. Impact on Css(free) Because K0 is unchanged and Cl is reduced by 50%,i Css(free) should double. Consequence You should anticipate significant side effects as a consequence of a higher free steady-state concentration of theophylline (Figure 9-8). Figure 9-9 demonstrates changes in plasma theophylline concentrations when enoxacin is begun and then later 1 discontinued. Considerations • Phenytoin is administered by intermittent intravenous administration. Impact on Css(free) BecauseK0 and Cl are unchanged,i Css(free) should remain unchanged. However, the total concentration necessary to achieve this therapeutic unbound concentration will be less than the normal reference range for phenytoin. Myocardial infarctions are known to significantly increase the concentration of alpha-1-acid glycoprotein (a serum globulin) and the protein binding of drugs associated with it. The protein binding of lidocaine is known to be high and primarily dependent on alpha-1-acid glycoprotein. Because lidocaine has a high extraction ratio and binds extensively to alpha-1-acid glycoprotein, Clh = Qh. Substituting for Css(total) Impact on Css(total) Because K0 and Qh are unchanged, Css(total) should remain unchanged. Impact on Css(free) Because K0 and Qh are unchanged and Fp is decreased, Css(free) should decrease, which could result in a reduced pharmacologic response (Figure 9-11). Consequence Because only total (bound and unbound) lidocaine concentrations can be measured clinically, you should anticipate a reduced pharmacologic response despite similar steady-state total lidocaine concentrations. This reduced response may necessitate high total lidocaine concentrations and a higher dose to achieve the desired response. These three examples represent how the well-stirred model and knowledge of the pharmacokinetic characteristics of a drug can be used to predict the effect of changes in hepatic blood flow, protein binding, and intrinsic clearance. These same principles can be used to assess a wide variety of clinically relevant situations. Changes in free and total steady-state plasma theophylline concentrations with the addition of cimetidine. The time period shown (60-360 hours) includes each of the three steady-state periods. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin. Change in free steady-state plasma lidocaine concentrations due to myocardial infarction. Some drugs are primarily excreted unchanged; others are extensively metabolized before excretion. The overall elimination rate is the sum of all metabolism and excretion processes and is referred to as total body elimination: total body elimination = drug excreted unchanged + drug metabolized Excretion is the process that removes a drug from tissues and the circulation. A drug can be excreted through urine, bile, sweat, expired air, breast milk, or seminal fluid. The most important routes of excretion for many drugs and their metabolites are the urine and bile. Excretion may occur for a biotransformed drug or for a drug that remains unchanged in the body. Renal excretion is the net effect of three distinct mechanisms within the kidneys: • glomerular filtration, • tubular secretion, and • tubular reabsorption. With glomerular filtration, blood flows into the capsule of the glomerulus and there is a passive diffusion of fluids and solutes across the porous glomerular membrane (Figure 9-13). In a healthy adult, up to 130 mL of fluid may cross the glomeruli per minute (total of both kidneys). Three factors influence glomerular filtration: • molecular size, • protein binding, and • glomerular integrity and total number of functioning nephrons. Drugs dissolved in the plasma may be filtered across the glomerulus; drugs that are protein bound or have a molecular weight greater than 60,000 are not filtered. Some drugs are actively secreted from the blood into the proximal tubule, which contains urine. These drugs (primarily weak organic acids and some bases) are excreted by carrier-mediated active processes that may be subject to competition from other substances in the body due to broad specificity of the carriers. If given together, probenecid competes with penicillin for secretion, so penicillin is secreted less rapidly (it has a longer half-life). This particular relationship can be used in therapeutic situations to extend the duration of penicillin action. This process occurs passively in the distal tubules for drugs that are lipid soluble or not highly ionized. For other agents, it can occur as an active process and (as with tubular secretion) is subject to competition from other agents. An example of reabsorption is glucose, which normally undergoes 100% reabsorption in the distal tubules of the kidneys. With renal dysfunction, glucose often is not reabsorbed and may appear in the urine. Other examples of agents that are actively reabsorbed include endogenous substances such as vitamins, electrolytes, and amino acids. Tubular reabsorption is dependent on the physical and chemical properties of the drug and the pH of the urine. Drugs that are highly ionized in the urine have less tubular reabsorption; they tend to stay in the urine and are excreted. Urea, for example, has a high tubular reabsorption at low urine flow rates and a low tubular reabsorption at high urine flow rates. Because renal clearance is determined by filtration, active secretion, and reabsorption, it is fairly complicated. However, because it is not easy to differentiate these processes when measuring the amount of drug in the urine, renal clearance is calculated from the ratio of the urine excretion rate to the drug concentration in plasma: There are several different methods to calculate renal drug clearance.