By L. Mitch. University of Medicine and Dentistry of New Jersey.
Its embryological origins remain a source of debate as the trigone was traditionally thought to be of mesodermal origin deriving from the common nephric duct and the ureter  generic 250 mg ampicillin with visa. In order for the ureteral bud to become incorporated into the developing urogenital sinus ampicillin 500mg cheap, the 320 common nephric duct must become absorbed into this sinus cheap ampicillin 500 mg line. Thus, it would stand to reason that at least part of the trigone is of mesodermal origin. Indeed, recent studies using transgenic mice suggest that in fact the trigone is of endodermal origin . Examination of murine models has demonstrated that the majority of the trigone is derived from detrusor muscle but interdigitating ureteral fibers do contribute to the final trigonal structure. These data were obtained via immunohistochemical analysis of both murine and human fetal tissue . Apoptosis plays an integral role in trigone formation; the common nephric duct undergoes apoptosis resulting in separation of the ureter from the Wolffian duct and apoptosis is required to create a patent ureteral orifice [43–45]. It is also likely that the final position of the ureteral orifice also depends on the growth of the bladder itself . The distal ureter starts to separate from the primitive bladder (ugs) by a terminal Wolffian duct segment, the common nephric duct (cnd). Broken yellow arrow shows the downward movement of the ureter toward the urogenital sinus. Yellow and green arrows indicate the final position of the distal ureter and Wolffian duct. Yellow and green arrows mark the position of the distal ureter and Wolffian duct before and after separation. Double-headed yellow arrow indicates epithelial wedge, an epithelial outgrowth, which facilitates the separation. Color code for (c, f, i): Wolffian duct and trigonal wedge, green; urogenital sinus, grey; Müllerian duct, pink; common nephric duct, red; kidney and ureter, blue. Once this signaling is initiated, the bud elongates to penetrate the blastema, and the process of branching begins. In order for the final form of a single human kidney to have 500,000 to 1 million nephrons, the ureteral bud must undergo branching morphogenesis (Figure 22. Iterative branching of the ureteral bud must occur about 15 times during human development in order to lead to this number of nephrons. As this division of the terminal ureteral bud takes place to produce a treelike structure, lateral branches differentiate into terminal bifid branches. In these terminal bifid branches, the ureteral bud tip will attach itself to a nephron and remove itself from further bifurcations. This attachment of the bud to a primitive nephron then initiates the formation of a full nephron. Critical to this view is the notion that the final population of nephrons is ultimately determined by the branching and proper functioning of the ureteral bud, a view espoused by Mackie and Stephens over 30 years ago . Equally critical to establishing normal renal function are the acquisition of the renal artery(ies) and subsequent vascular development (for a more detailed review of renal development, the reader is referred to Shah ). The caudal end of the Wolffian duct is incorporated into the developing bladder (red arrow). The yellow-marked region contributes to the trigone, the green one to the urethra, and blue for the lateral bladder. This ectopic ureter opens into the urethra with the abnormal outflow and development of hydroureter. There is also a role for retinoic acid–mediated signaling in the development of the ureteral buds and trigone as shown in a model using targeted deletion of the retinoic acid receptors . This is crucial for normal development since fetal urine serves as amniotic fluid, which is essential for normal lung development. These proved to be reversible upon reimplantation of the ureters into the bladder. Urinary diversion in the fetal sheep model was also associated with altered patterns of collagen expression  and decreased cell proliferation and apoptosis  in the bladder wall. Thus, there is ample support for the concept that mechanical distention is an essential contributor to normal bladder development. This is supported by the clinical observations in patients with bilateral ectopic ureters and bladder exstrophy, which are two conditions in which the bladder wall fails to cycle. Both conditions are characterized by small-capacity bladders and poor wall compliance. Contraction of the bladder is mediated by the pelvic nerve that arises from the sacral segments S2,3,4. Given their common embryological origins, it is not surprising that sensory fibers from the rectum are also directed to the same segments. Experimental work done in rat models using viral vectors expressing red or green fluorescent proteins has shown that there is a cross talk between these two organ systems. As an example using modified pseudorabies virus tagged to express green fluorescent protein injected into the bladder and the modified pseudorabies virus tagged to express beta galactosidase in the rectum, Rouzade-Dominguez et al. Many of the nuclei in Barrington’s nucleus were stained either green (reflecting sensory input from the bladder) or red (reflecting sensory input from the rectum because the beta galactosidase was visualized with an antibody tagged with red fluorescent protein). However, when imaged under dual fluorescent conditions, a substantial fraction of these nerves stained yellow indicating that these individual nerves were receiving sensory input from both the bladder and the rectum. This image is of clinical relevance because constipation is a major contributing factor to bladder dysfunction because it can affect both the sensory and motor pathways. Evidence for this comes from ample clinical observations that children with incontinence improve following treatment of their underlying constipation . Further evidence comes from a clinical study of women undergoing urodynamic evaluations in which a balloon catheter was placed in the rectum; the results of the urodynamic parameters varied substantially once the balloon was inflated to mimic the rectal distention seen with constipation . These neurons were labeled with pseudorabies virus expressing green fluorescent protein that was injected into the bladder (green) and pseudorabies virus expressing β-galactosidase (red) that was injected into the distal colon. A substantial population of these neurons are labeled with both viruses appearing as either yellow or orange (arrows) or cells that have a red nucleus and green cytoplasm (arrowheads). In these patients, the urethra and the vagina converge in a short common channel, and the convergence is close to the perineum. In some cases, the voided urine is trapped within the vagina, resulting in hydrocolpos.
The ultimate improvement would be a package consisting of a 5 mm motorized stereoscopic videoendoscope purchase ampicillin 500 mg mastercard, dominant handheld 5 mm motorized needle holder buy generic ampicillin 500 mg on-line, and 3 mm nondominant handheld instrumentation buy ampicillin 500mg visa. That would offer to institutions and countries that cannot consider larger capital investments a decent platform coming at a fraction of the cost, footprint, and skin incisions of those implied with the larger robotic systems. Under the latter perspective, the next generation of multiarm robotic systems follows a size reduction pathway, which is also excellent news for the future of vesicoscopy. Combined vaginal and vesicoscopic collaborative repair of complex vesicovaginal fistulae. Grange P, Qteishat A, Makanjuola J, Khan A, Rouse P, Kouriefs C, Brown C, Ahyai S, Chun F. Air insufflation versus water irrigation during flexible cystoscopy: A prospective randomized study. Endoscopic cross-trigonal ureteral reimplantation under carbon dioxide bladder insufflation: A novel technique. A simple and safe technique for trocar positioning in vesicoscopic ureteric reimplantation. In-utero percutaneous cystoscopy in the management of fetal lower obstructive uropathy. Video-assisted percutaneous cystoscopy of the bladder and prostatic urethra in the dog: New approach for visual laser ablation of the prostate. Transvesicoscopic Cohen ureteric reimplantation for vesicoureteral reflux in children: A single-centre 5-year experience. A new technique for laparoscopic aortobifemoral grafting in occlusive aortoiliac disease. Hand assisted laparoscopic bilateral nephroureterectomy in 1 session without repositioning patients is facilitated by alternating inflation cuffs. Extraperitoneal laparoscopic para-aortic lymph node dissection for early stage nonseminomatous germ cell tumors of the testis with introduction of a nerve sparing technique: Description and results. Fifth Leading Light in Urogynaecology Meeting of the European Urogynaecological Association, 2012 Podium, Spain. Interposition flaps in transabdominal vesicovaginal fistula repairs: Are they really necessary? Vesicoscopic cross-trigonal ureteral reimplantation: A minimally invasive option for repair of vesicoureteral reflux. Eldred-Evans D, Grange P, Cheang A, Yamamoto H, Ayis S, Mulla M, Immenroth M, Sharma D, Reedy G. The majority of the evidence comparing standard, laparoscopic, and robotic approaches relates to sacrocolpopexy. The minimally invasive approach is considered to have advantages, which include a shorter hospital stay, faster recovery, and return to normal activity. Prolapse is one of the most common indications for surgery in women, with over 200,000 procedures per year for the condition in the United States . In Europe in 2005, the number of admissions for prolapse surgery was 36,854 in Germany, 36,679 in France, and 28,959 in the United Kingdom. The estimated costs associated with these admissions were €144 million, €83 million, and €81 million in the three countries, respectively . With an aging and active population, the demand for services related to female pelvic floor dysfunction is likely to continue to rise, with an increasing burden on health-care budgets. The last two decades have seen significant changes in the pattern of prolapse surgery worldwide, with a move toward more minimally invasive treatments. The minimally invasive approach is considered to be advantageous as it is associated with reduced pain, bleeding, hospitalization, and recovery time, with improved cosmetic results. Sacrocolpopexy, first described via the abdominal route in 1957, is considered to be one of the most effective and durable operations for apical vaginal prolapse  with reported long-term success rates of 78%–100% . Despite the advantages of sacrocolpopexy, vaginal vault surgery is more often performed because it is faster, is less painful, allows a rapid recovery, and is cheaper. Laparoscopic sacrocolpopexy, first described in 1994 , has been adopted by pelvic floor surgeons to address concerns about morbidity and to shorten postoperative recovery. Success rates for the open and laparoscopic routes have been shown to be comparable  with reduced blood loss and a similar operating time. However, the laparoscopic route requires high levels of laparoscopic skills as it involves extensive dissection and suturing. Laparoscopic instruments have a limited range of movement in the abdominal cavity. Manipulation of the instruments for suturing and knot tying in the pelvis is technically challenging. Adoption has therefore been limited despite the clinical advantages of the laparoscopic route. Robotic technology has made laparoscopic sacrocolpopexy a more feasible operation for many surgeons as it offers enhanced visualization, an increased range of movement of instruments and improved ergonomics for the surgeon. Some argue that it more closely approximates to the open technique and is therefore easier for the surgeons who do not have advanced laparoscopic skills to learn, with a shorter learning curve. There has been a rapid adoption of robot-assisted surgery across surgical specialties, particularly in the United States. The number of robotic procedures performed worldwide almost tripled between 2007 and 2010, from approximately 80,0 to 205,000 . By 2014, over 3000 robots had been installed worldwide and over half a million procedures performed (http://www. Uptake has been greatest in urology and gynecology and these specialties perform the majority of robotic surgeries . Enthusiasm for technological innovation by both surgeons and patients often leads to rapid adoption before efficacy and safety is established relative to existing procedures. This may be due to a higher cost of the new procedure or that its introduction results in more patients being treated overall. This is particularly pertinent when the procedure is relatively easy to learn and applicable to a large number of patients. While uptake of laparoscopic sacrocolpopexy has been relatively slow, due to the technical difficulty involved in learning the procedure, robotic surgery is perceived as easier to learn, and uptake of robotic sacrocolpopexy has been rapid in countries with access to the technology.
Sites 43 and 53 are epicardial sites The bar represents duration of the electrogram buy cheap ampicillin 500 mg. Note that the low-amplitude late potential (arrow) is associated with late endocardial activity from four sites and late epicardial activity from one site discount ampicillin 500 mg visa. Relation between late potentials on the body surface and directly recorded fragmented electrograms in patients with ventricular tachycardia safe ampicillin 500mg. Differences in excitability, refractoriness, and dispersion of refractoriness are other potential arrhythmogenic abnormalities. We evaluated the effects of infarction on the threshold of excitability, refractoriness, and strength- 106 interval curves. These studies demonstrated that sites of infarction characterized by abnormal electrograms have higher thresholds than normal sites in patients with infarction (1. This higher threshold corresponds to a strength-interval curve that has shifted upward, particularly during late coupling intervals (Fig 11-37). Refractory periods determined at threshold were longer at sites of infarction, but the steep part of the strength-interval curves were not significantly different (Fig 11-38). Furthermore, the effect of change in cycle length of the refractory period measured as the steep part of the strength-interval curve was similar in normal sites and sites of infarction (39 ± 9 vs. The current at which the steep part of the strength-interval curve was achieved was also comparable. The X denotes measurements from a normal site and O from an infarcted site from the infarct patient group. Electrophysiologic sequelae of chronic myocardial infarction: local refractoriness and electrographic characteristics of the left ventricle. This was true whether or not the parameters were evaluated for the entire left ventricle or at adjacent sites. Thus, one must consider abnormalities of conduction to be of primary importance in the genesis of sustained uniform ventricular arrhythmias. The greater these abnormalities, the more likely uniform tachycardias occur spontaneously or can be induced. Invasive or noninvasive methods to demonstrate abnormalities of conduction are, therefore, useful markers of an arrhythmogenic substrate. The strength-interval curves measured at each site are also shown with the measured refractory period plotted from threshold to 10 mA. Alterations characteristic of chronic infarction are seen in both the local electrogram and strength-interval curve. Electrophysiologic sequelae of chronic myocardial infarction: local refractoriness and electrographic characteristics of the left ventricle. Electrophysiologic sequelae of chronic myocardial infarction: local refractoriness and electrographic characteristics of the left ventricle. On the horizontal axis is time duration and on the vertical axis are the mapped left ventricular sites. The right-hand edge of each bar represents the end of total recovery time (the sum of activation time and local refractoriness). Most of the recent knowledge of cellular mechanisms of arrhythmias are derived from isolated atrial, Purkinje, ventricular muscle fibers, and P. More recently molecular genetics has provided information relevant to the mechanisms of certain arrhythmias. The exact mechanism by which these ion channelopathies cause arrhythmias is unresolved and is under active investigation. Debate therefore continues as to the role of early afterdepolarizations, abnormal automaticity, and reentry in these polymorphic tachycardias that are the hallmark of these syndromes. This is particularly true in the Brugada syndrome in which controversy remains as to 120 121 whether it is a problem of conduction or repolarization. However, dispersion of refractoriness is 90 msec (the longest refractory period being 320 msec at site 1). Because of the irregular and prolonged activation times, there is prolongation of total dispersion of recovery of 15 msec. Despite the differences in experimental design, in my opinion, generalizations regarding arrhythmia mechanisms can be made by comparing the mode of initiation of tachycardias and influence of stimulation during tachycardias in in vitro and in vivo experimental preparations to comparable situations in humans. The bulk of evidence derived from these studies, albeit indirect, suggests that reentry is the mechanism of sustained uniform 1 122 123 tachycardias associated with coronary artery disease. Moreover, their response to programmed stimulation and pharmacologic agents suggests a common mechanism. How these responses differ from those expected for other mechanisms is discussed in more detail subsequently. Table 11-7 Data Based on Adjacent Left Ventricle Sites Endocardial Activation Dispersion of Dispersion of Total Time (msec) Refractoriness (msec) Recovery Time (msec) Normal left ventricle (no ventricular 25 ± 7 32 ± 11 41 ± 14 tachycardia) Coronary artery disease (with 42 ± 11 75 ± 41 42 ± 20 ventricular tachycardia) p <0. While infarction provides gross fibrosis and macro nonuniform anisotropy, abnormal propagation in cardiomyopathies with less fibrosis may be related to the abnormalities of gap junction number, structure, function, and location. Tachyarrhythmias that are believed to be due to early afterdepolarization are bradycardia dependent, and although they can be initiated in the experimental laboratory, they are not well suited for study by programmed stimulation, which automatically necessitates a relative “tachycardic” 125 126 129 130 state. As such I do not believe this mode of stimulation can distinguish triggered activity from reentrant rhythms. Some even report the results in patients who have never had a sustained arrhythmia, but who might be at risk for its occurrence. As mentioned earlier in this chapter, the anatomic and 22 23 32 89 95 electrophysiologic substrates of these arrhythmias differ. Therefore, sensitivity and specificity should only be applied to the use of programmed stimulation for a single arrhythmia type. In addition to the type of arrhythmia and the underlying anatomic substrate, specific features of the methodology of programmed stimulation can influence the ability to initiate the tachycardia. They include distance from the origin of the arrhythmia, refractoriness at the site of stimulation, and conduction to the potential site of the tachycardia circuit or focus. Thus, although some generalities exist regarding the effects of increasing number of extrastimuli, altering drive cycle lengths, and increasing current, the investigator must interpret the response to programmed stimulation in light of the specific arrhythmia being evaluated or whether stimulation is being used for risk stratification postmyocardial infarction. In general, the greater the number of extrastimuli employed, the increased sensitivity of induction of any arrhythmia; however, this is associated with a decreasing specificity of the technique (Fig. The various modes of initiation are shown on the horizontal axis from least to most aggressive, and the percentage of inducibility rate is shown on the vertical axis. It can be seen that the more aggressive the stimulation, the higher the sensitivity but the lower the specificity.
Delayed hypersensitivity: This type of voked by many antigens; the cause of hy- hypersensitivity include the following: persensitivity reaction will vary from one ∙ Type 4: Hypersensitivity buy 250mg ampicillin free shipping. Type 4 reaction This class of antibody is cytophilic in nature involves T cell recognition and because of and has got high affinity for the fragment longer time course discount ampicillin 500mg online, this is referred to delayed crystallizable (Fc) receptors on the surface type of hypersensitivity reaction buy ampicillin 500 mg. A subsequent exposure HyperSenSitivity to same allergen cross-links the membrane Type I hypersensitivity reaction is induced bound IgE on the sensitized mast cell or ba- by certain types of antigens known as aller- sophil causing degranulation of these cells gens and has all the hall marks of a normal (Fig. The allergens induce a humoral response by the same mechanism, Following degranulation, there is libera- as antigens generating antibody-secreting tion of pharmacologically active mediators to plasma cells and memory cells. The main actions of difference is that in response to allergens, the these mediators are vasodilation and smooth plasma cells secrete immunoglobulin E (IgE). The secreted IgE molecules bind to IgE specific Fc receptors on mast cells and blood basophils (many molecules of IgE with various specificities can bind to the IgE specific Fc receptor). Second exposure to the allergen leads to cross-linking of the bound IgE, triggering the release of pharmacologically active mediators, such as vasoactive amines from mast cells and basophils. The mediators cause smooth muscle contraction, increased vascular permeability and vasodilatation. Allergens Reaginic Antibody (IgE) Immunoglobulin E is produced in large quan- Allergy is mediated by IgE. The serum The level of IgE remains high, as long as the from Kushner (who was allergic to fish) was parasite survives in the host. When sub- may have an abnormality called atopy, a he- sequently the fish antigen was injected to reditary predisposition to the development of the sensitized site, there was an immedi- immediate type of hypersensitivity reaction ate wheel and flare reaction. In Kushner proposed the existence of atopic this condition, abnormally there is high IgE reagin in the allergic individuals. Ishizaka showed that the atopic reagin is a Hence, the term allergen refers specifically to new class of immunoglobulin called IgE. Mast cells are found throughout connective The high level of IgE is partly genetic, but tissue particularly, near blood and lymphatic often familial. High concentrations of mast cells are there is also marked degree of eosinophilia. Electron mi- to a region that encodes the β chain of high- crograph reveals a multilobed nucleus, few affinity IgE receptors. After activation, these mediators, The common allergens are proteins (foreign in both mast cells and basophils are released serum, vaccine), plant pollens (ryegrass, rag- causing the clinical manifestations of the type weed, timothy grass, etc. Any mast cell or 146 Textbook of Immunology basophil may contain either of these two re- is essential for degranulation of mast cells or ceptors. This cross-linking transmits a signal that tiates the process of mast cell degranulation. Allergen cross-linkage of IgE bound ma membrane discharging their contents to the exterior. Simultaneously, there is the induction of synthesis of newly formed mediators from Mechanism of arachidonic acid, leading to the production of IgE-mediated Degranulation prostaglandins and leukotrienes, which have Although, mast cell degranulation gener- a direct effect on local tissues. In the lung, ally initiated by allergen cross-linkage of the they cause immediate bronchoconstriction, bound IgE, a number of other stimuli can also mucosal edema and hypersecretion leading initiate the process, including the anaphyla- to asthma. When these mediators initiate ben- one molecule of IgE (monovalent IgE) fixed eficial effect against parasitic infections, per- on the mast cells, apparently there is no ef- mitting the influx of plasma and inflamma- fect on the target cell. It is only after aller- tory cells to the pathogen by vasodilatation gens cross-links the fixed IgE complex then and increased vascular permeability. Mast cell activa- tion can be produced by immunological stimuli, which cross-link Fc receptors and by other agents such as anaphylatoxins and secretagogues (e. The common features in each case is the influx of Ca2+ ions into the mast cell, which is crucial for degranulation. Microtubule formation and movement of the granules to the cell membrane lead to fusion of the granule with the plasma membrane and the plasma membrane associated with activation of phospholipase A2, release of arachidonic acid; this can then be metabolized by lipoxygenase or cyclooxygenase enzymes, depending on the mast cell type. Both, the preformed granule-associated lipid mediators and the newly formed granule-associated lipid mediators have three main areas of action. Chemotactic agents: A variety of cells are attracted to the site of mast cell activa- tion, in particular eosinophils, neutrophils and mononuclear cells including lymphocytes. In addition, recent evidence suggests that certain of the preformed cytokines released from degranulating mast cells are also chemotactic for inflammatory cells; 2. Tryptase, the major neutral pro- tease of human lung mast cells, can activate C3 directly; this function is inhibited by heparin. Kininogenase are also released and these affect small blood vessels by generating kinins from kininogens, again leading to inflammation; 3. Spasmogens: They have a direct effect on bronchial smooth muscles, but could also increase mucus secretion leading to bronchial plugging. Enhanced Ca2+ influx stimulated by an ionophore that increases membrane permeability to Ca2+ ions. Note that mechanisms the B, C and D do not require allergen; mechanisms of E and F require neither allergen nor IgE and the mechanism of F does not even require receptor cross-linkage. Primary platelet-activating factor, leukotrienes, pros- mediators are preformed, but stored in the taglandins, bradykinins and various cytok- granules (histamine, proteases, eosinophil ines. The main biological activities of some chemotactic factor, neutrophil chemotactic of the mediators are described subsequently. The secondary mediators Histamine: It is an inflammatory media- are either synthesized following, cross-link- tor and found preformed in the granules of ing or released due to breakdown of phos- mast cells and basophils. Histamine H3 binding of histamine affects synthesis and once released after degranulation binds to release of histamine. The the mast cell undergoes degranulation and binding induces contraction of intestinal and the enzymatic breakdown of phospholipids. An ensuing enzymatic cascade gen- Antihistamine drugs used to treat allergies, erates the prostaglandins and leukotrienes. In contrast, binding of histamine to H2 receptors augments gastric Arachidonic acid: It is a fatty acid, which can acid secretion and airways mucus produc- be liberated from membrane phospholipids tion. Binding of histamine to H2 receptors by the action of phospholipase (phospholi- on mast cells and basophils suppresses de- pase A2). Once liberated, arachidonic acid granulation; thus, histamine exerts negative can be metabolized by either the cyclooxy- feedback on the release of the mediators. IgE are dependent on several factors such as: The leukotrienes mediate bronchoc- 1. The effect of antigen dosage and mode onstriction, increased vascular permeabil- of antigen presentation, influence the ity and mucus production.