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Clinical and urodynamic assessment of the porcine dermis bladder sling in the treatment of genuine stress incontinence order cheap malegra dxt plus line erectile dysfunction foods that help. Comparative analysis of urinary incontinence severity after autologous fascia pubovaginal sling generic malegra dxt plus 160mg amex zinc causes erectile dysfunction, pubovaginal sling and tension-free vaginal tape buy discount malegra dxt plus 160 mg on-line penile injections for erectile dysfunction side effects. Porcine small intestinal submucosa as a percutaneous mid-urethral sling: 2- year results buy malegra dxt plus paypal erectile dysfunction case study. Small intestinal submucosa for pubourethral sling suspension for the treatment of stress incontinence: First histopathological results in humans. Intense inflammatory reaction with porcine small intestine submucosa pubovaginal sling or tape for stress urinary incontinence. Minimally invasive synthetic sling suburethral sling operations for stress urinary incontinence in women. Deux incontinence apres adenonectomie queries par injection de paraffine daris de perinee. Transurethral polytetrafluoroethylene injection in female patients with urinary continence. Disappointing effect of endoscopic teflon injection for female stress incontinence. Pulmonary teflon granulomas following periurethral teflon injection for urinary incontinence. Pulmonary migration following periurethral polytetrafluoroethylene injection for urinary incontinence. Long-term follow-up of women treated with periurethral teflon injections for stress incontinence. Endoscopic injection of autologous adipose tissue in the treatment of female incontinence. Treatment of urinary stress incontinence using paraurethral injection of autologous fat. Periurethral injection of autologous fat for the treatment of sphincteric incontinence. Periurethral autologous fat injection as treatment for female stress urinary incontinence: A randomized double-blind controlled trial. A diagnosis of urodynamic stress incontinence can only be made after urodynamic investigation, and this is defined as the involuntary leakage of urine during increased abdominal pressure in the absence of a detrusor contraction [1]. Stress incontinence is the most commonly reported type of urinary incontinence in women. In a large epidemiological study of 27,936 women from Norway [2], overall, 25% of women reported urinary incontinence, of whom 7% considered it to be significant, and the prevalence of incontinence increased with age. When considering the type of incontinence, 50% of women complained of stress, 11% urge, and 36% mixed incontinence. The prevalence of urinary incontinence among nulliparous women ranged from 8% to 32% and increased with age. In general, parity was associated with incontinence, and the first delivery was the most significant. There was a similar association for mixed incontinence although not for urge incontinence [3]. The bladder neck and proximal urethra are normally situated in an intra-abdominal position above the pelvic floor and are supported by the pubourethral ligaments. Damage to either the pelvic floor musculature (levator ani) or pubourethral ligaments may result in descent of the proximal urethra such that it is no longer an intra-abdominal organ, and this results in leakage of urine per urethram during stress. This theory has given rise to the concept of the “hammock hypothesis,” which suggests that the posterior position of the vagina provides a backboard against which increasing intra-abdominal forces compress the urethra [4]. This is supported by the fact that continent women experience an increase in intraurethral closure pressure during coughing [5]. This pressure rise is lost in women with stress incontinence although it may be restored following successful continence surgery [6]. In order to distinguish this type of stress incontinence from that caused by descent and rotation of the bladder neck during straining, the Blaivas Classification has been described based on videocystourethrographic observations [7]. More recently, the “midurethral theory” or “integral theory” has been described by Petros and Ulmsten [10]. This concept is based on earlier studies suggesting that the distal and midurethra play an important role in the continence mechanism [11] and that the maximal urethral closure pressure is at the mid-urethral point [12]. This theory proposes that damage to the pubourethral ligaments supporting the urethra, impaired support of the anterior vaginal wall to the mid-urethra, and weakened function of part of the pubococcygeal muscles, that insert adjacent to the urethra, are responsible for causing stress incontinence. This association of urethral hypermobility and stress urinary incontinence was also noted by Watson in 1924 [14] although it was not until 1949 that the first retropubic procedure for stress incontinence was described by Marshall et al. This early example of cooperation between two urologists and a gynecologist described “the correction of stress incontinence by simple vesicourethral suspension” in a series of 50 patients including 12 men with postprostatectomy stress incontinence. They reported an initial 82% success and 7% improvement rate, and the procedure became popular in the management of women with stress urinary incontinence. In 1961, John Burch described his modification of the Marshall–Marchetti–Krantz procedure when he encountered difficulty in suture placement. Rather than placing the sutures in the periosteum of the pubic symphysis, he described the attachment of the anterolateral vagina to the pectineal ligament using three sutures on each side [16]. He initially reported a series of 53 patients with 100% success rate and subsequently published a 9-year series of results in 1968 with a 93% success rate and an 8% incidence of enterocele [17]. Over the last 50 years, the Burch colposuspension has remained an efficacious and durable procedure in the surgical management of stress urinary incontinence and has undergone several modifications. This observation led to the widely adopted technique of providing support to the bladder neck without overelevation. Although many authors have reported excellent short-term subjective results from laparoscopic colposuspension [21], early studies showed inferior results to the open procedure [22,23]. More recently, the description of the “integral theory” has revolutionized the concept behind the traditional approach to retropubic surgery and has led to the introduction of the mid-urethral tapes using a retropubic [24,25] and transobturator approach [26]. While these procedures have largely replaced retropubic urethropexies in clinical practice, the colposuspension still has an important role in the management of women with stress urinary incontinence. The bladder neck and proximal urethra are then mobilized from the vagina with the assistance of the index and middle fingers of the surgeon’s left hand placed within the vagina. Each suture should include the paraurethral tissue, lateral wall of the urethra, and the vaginal wall. The sutures are then fixed to the periosteum of the superior pubic ramus or the perichondrium of the symphysis pubis. Further sutures may then be placed between the anterior surface of the bladder and rectus abdominis to provide additional elevation and support (Figure 71. At the end of the procedure, a Redivac drain should be placed in the retropubic space and a suprapubic catheter used for postoperative urinary drainage. Results Overall, there have been 58 published papers between 1951 and 1998 that have included 3238 patients, although many of these studies were retrospective case series. Overall cure rates were approximately 88% with results of 92% and 84% in primary surgery and redo surgery, respectively [27]. While there has been no formal Cochrane Review of the procedure, there has been a review of comparative trials with colposuspension [28–30]. Two of these long- term studies have shown the efficacy rates to reduce over time with reported success rates being 90% and 77% at 1 year, 86% and 57% at 5 years, and 72% and 28% at 10 years [34,36]. Patients present with a history of severe suprapubic pain 1115 radiating into the groins and perineum, and a bone scan shows increased uptake in the suprapubic region. Long-term antibiotic treatment over several months is generally required, and occasionally, a retropubic abscess may require drainage. Colposuspension Operative Technique The patient is positioned on the operating table in the modified lithotomy position using Lloyd–Davies stirrups. The abdomen and vagina are then prepared as a sterile operating field in order to allow the manipulation of the vaginal fornices and bladder neck by the surgeon. An indwelling Foley catheter is then inserted and the balloon inflated with 6 mL of water to allow the identification of the bladder neck. A low transverse suprapubic incision approximately 1 cm above the pubic symphysis is made and the rectus fascia incised taking care not to open the peritoneal cavity unless a concomitant intra-abdominal procedure is being performed. Vaginal manipulation is also used to further assist in the elevation of the lateral vaginal fornices while the bladder is swept medially. Two to four delayed absorbable sutures are inserted into the paravaginal fascia on each side and each tied down onto the vaginal tissue ensuring hemostasis. The suture is then passed vertically through the ipsilateral iliopectineal ligament, taking care not to pull the bladder neck open, and left untied. Once all the sutures are positioned correctly, each lateral fornix is elevated by an assistant allowing the sutures to be tied easily without tension (Figure 71. After checking for adequate hemostasis, the retropubic space is drained with a Redivac suction drain and the abdomen closed (Figure 71. The bladder is left on free drainage using a suprapubic catheter for 48 hours prior to starting a clamping regimen. When the urinary residuals are less than 100 mL, the suprapubic catheter may be removed. When considering all studies of colposuspension, objective cure rates varied between 59% and 100% (median 80%) and subjective cure rates between 71% and 100% (median 88%). Based on these results, colposuspension would appear to have comparable objective and subjective outcomes to traditional sling procedures and to both retropubic and transobturator mid-urethral tapes. The evidence would also appear to suggest that outcomes with colposuspension are significantly better than those achieved with anterior colporrhaphy, needle suspension procedures, paravaginal repair, and the Marshall–Marchetti– Krantz procedure. Outcome: Colposuspension Historically, there have been many prospective case series and cohort studies assessing the efficacy of colposuspension with some studies providing long-term follow-up data up to 20 years (Table 71. The first of these was reported by Jarvis in 1994 [41] who reviewed 1726 women with a follow-up of at least 1 year and a mean objective success rate of 84. Very similar results were reported from a meta-analysis of 2196 women reported by the American Urological Association in 1997. More recently, the Cochrane group has published a meta-analysis of 39 randomized controlled trials involving 2403 women with a mean follow-up of 1 year.

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Moderate renal impairment and mild hepatic impairment have little impact on drug metabolism and are not clinically important [308] order malegra dxt plus online now erectile dysfunction usmle. The treatment groups received either 100 or 150 mg twice daily and experienced a significant reduction in micturition frequency buy genuine malegra dxt plus erectile dysfunction in 20s, incontinence episodes buy malegra dxt plus 160mg free shipping erectile dysfunction 50 years old, and urgency symptoms purchase malegra dxt plus 160 mg otc erectile dysfunction homeopathic treatment, as well as an increase in volume voided. The drug was well tolerated in this study with the most common side effects being headache and gastrointestinal effects. Dose-dependent improvements in micturition frequency and volume voided were noted. After 12 weeks, both treatment groups demonstrated a statistically significant decrease in micturition frequency and incontinence episodes compared to placebo. The drug was well tolerated with similar rates of adverse events in the treatment and placebo groups. Both doses of mirabegron achieved statistically significant improvement in urgency incontinence episodes and micturition frequency over placebo. Post hoc subgroup analysis of this cohort was performed to assess the response to mirabegron in patients who had tried prior antimuscarinic agents [325]. Similar treatment benefit was noted in treatment-naïve patients and those who had discontinued prior antimuscarinic agents due to poor efficacy. This study demonstrated that mirabegron 25 and 50 mg were effective in reducing urgency incontinence episodes and micturition frequency in this population and were well tolerated. The drug was available in Japan several years before obtaining approval in the United States; the Japanese label contains a warning advising against the use of the drug in patients of reproductive age. Terbutaline Terbutaline, a β -agonist, has been reported to have a beneficial clinical effect at an oral dose of 5 mg2 three times a day [126]. In nine patients, transient side effects including palpitations, tachycardia, or hand tremor occurred. These effects include facilitating urine storage by decreasing bladder contractility and increasing outlet resistance. They have anticholinergic effects both centrally and peripherally, and they block the reuptake of serotonin and noradrenaline [133]. The most common side effect includes nausea, followed by dry mouth, dizziness, constipation, insomnia, and fatigue. Whether the same toxicity profile exists for these drugs at the lower dose remains to be seen. There was a near significant decrease in urine loss measured by pad weight and in cystometric parameters of first sensation and maximum bladder capacity. Doxepin treatment was preferred by 14 of the 19 patients, while 2 preferred placebo and 3 had no preference. The data to support its role in increasing outlet resistance will be presented later. The product information for this drug contains a black box warning due to increased suicidal thinking and behavior in those taking the drug for psychiatric disorders. Imipramine has prominent systemic anticholinergic effects but only a weak antimuscarinic effect on bladder smooth muscle [138]. Clinically, imipramine seems to be effective in decreasing bladder contractility and increasing outlet resistance. In those patients who underwent repeated cystometry, bladder capacity increased by a mean of 105 mL and bladder pressure at capacity decreased by a mean of 18 cmH O. A combination of low-dose imipramine and an antimuscarinic or an antispasmodic has been reported as useful for decreasing bladder contractility and detrusor pressure in some neurogenic patients [141]. A proper risk–benefit analysis of imipramine in a good-quality clinical trial has not been performed. The results showed a significant reduction in micturition frequency in men; however, the remainder of assessed outcomes showed a trend toward improvement without reaching significance. Intravesical administration allows for high concentrations of the agent to reach the bladder tissue without systemic administration and resultant unsuitable levels in other organs. The vast majority of intravesical experience has been with 726 ® ® ® Botox , with no bladder experience reported for Xeomin. Under direct cystoscopic visualization using a 6F injection needle, 30 injections of 1 mL each were administered to the bladder wall in 30 different locations above the trigone [150]. Since that description, several other authors have described varying doses, dilutions, number of sites, and locations (trigone, suburothelial space) [151]. This dose reduction was felt to appropriately balance the efficacy of treatment with risk of incomplete bladder emptying or urinary retention. There remains quite a bit of variability in dilution volume, injection volume, and number and location of injection sites. This study also showed no clinically relevant difference in the efficacy or duration of effect between 200 and 300 U. Significant improvements in maximum cystometric capacity, frequency, and incontinence episodes were seen at 4 and 12 weeks. The duration of retention following the first injection was approximately 2 months; however, following repeat injection, this duration increased to 5 months. Doses of 100 U and greater were found to demonstrate durable efficacy with doses greater than 150 U contributing minimal additional benefit. It was noted that clinical improvements and improvements in urodynamic parameters generally trended together. No difference was detected in reduction of urgency incontinence episodes between the two groups. One month after treatment with 200 U, 76% of patients reported greater than 50% improvement in symptoms. Further studies are needed to determine optimum dosage, location, and methods of injection. Polysynaptic Inhibitors Baclofen Baclofen depresses synaptic excitation of motor neurons in the spinal cord and normalizes interneuron activity [159]. Intrathecal baclofen has been shown to be useful in some patients with spasticity and bladder dysfunction [161]. Side effects of baclofen include drowsiness, vertigo, insomnia, weakness, ataxia, slurred speech, and psychiatric disturbances [162]. Other Potential Agents Estrogen The hormonally sensitive tissues of the bladder, urethra, and pelvic floor may play a role in voiding mechanisms. Two types of estrogen receptors (α and β) have been identified in the trigone of the bladder, urethra, vagina, levator ani muscles, pelvic fascia, and the supporting ligaments [163]. In fact, all four layers of the urethra (epithelium, vasculature, connective tissue, and muscle) are estrogen sensitive and thought to play a role in maintaining positive urethral pressure. Menopause causes marked decline in the presence and expression of both α- and β-receptor subtypes. Epidemiological studies have implicated estrogen deficiency, as a result of menopause, in the etiology of voiding symptoms that occur as women age. One difficulty in interpreting the available conflicting data on the topic is the use of several difference estrogen preparations, doses, routes of administration and the inconsistent use of concomitant progesterone. There is good evidence that urogenital atrophy, both the symptoms and cytological changes, can be reversed by treatment with low-dose vaginal estrogen. In the ovariectomized rabbit, estrogen replacement has been shown to decrease muscarinic receptor density thereby diminishing contractile response [167]. Estradiol has also been found to reduce the frequency and amplitude of rabbit spontaneous rhythmic detrusor contractions [168]. After 3 months of treatment, they were unable to show objective evidence of a reduction in urinary frequency or urgency. The authors hypothesized that the symptomatic improvement in this group was likely related to the treatment of their urogenital atrophy. Statistically, significant improvements in urinary frequency, urgency, number of incontinence episodes, first sensation to void, and bladder capacity were found for patients taking estrogen therapy. Separate analysis for systemic and locally applied estrogen revealed that local therapy, but not systemic, had a significant beneficial effect on all outcome variables. Systemic estrogen did have a beneficial impact on incontinence episodes and first sensation to void. Common adverse effects include anxiety, insomnia, irritability, mood disturbances, melasma, rash, pruritus, breast enlargement, breast pain, increase in high-density lipoprotein cholesterol and triglycerides, glucose intolerance, hot flashes, change in libido, dysmenorrhea, vaginal discharge, and arthralgias. Unopposed estrogen in postmenopausal women increases the risk of endometrial carcinoma by 5–15-fold. The risk of thromboembolic disease is clearly elevated in women taking oral estrogens with a history of preexisting cardiovascular disease [172]. Regardless, estrogen replacement has produced conflicting results in improving symptoms. Most authors believe that urogenital atrophy is the result of estrogen deficiency and responds well to estrogen replacement, especially locally. In some cases, irritative urological symptoms (usually in combination with vaginal symptoms) may result from atrophy and may respond to estrogen therapy [173]. Gabapentin 729 Gabapentin was originally designed as an anticonvulsant, but now has expanded indications for neuropathic pain, anxiety, and sleep disorders [174]. Of these patients, 8 were still on the drug 1 year later with persistent efficacy. Adverse effects of gabapentin include somnolence, dizziness, ataxia, fatigue, diarrhea, tremor, and nystagmus [177]. Further studies that include a clarification of the recommended dosages are needed. The drug significantly decreased micturition frequency and number of urgency episodes as reported on a 4–10-day voiding diary. Despite statistical significance, the clinical significance of these findings is questionable.

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It is often difficult to determine whether the recorded His deflection is antegrade or retrograde—or for that matter whether an apparent His bundle deflection is really a right bundle branch potential order malegra dxt plus with a visa erectile dysfunction drugs and alcohol. Two techniques that may be used to clarify the situation are (a) recording right and left bundle branch potentials to demonstrate that their activation begins before His bundle activation and (b) His bundle pacing producing a longer H-V interval than the one noted during the tachycardia cheap 160mg malegra dxt plus mastercard alcohol and erectile dysfunction statistics. Both of these are extremely difficult to do but can help define the mechanism of His bundle activation and the tachycardia origin discount 160mg malegra dxt plus with mastercard erectile dysfunction kya hota hai. The simplest methods for verifying proper catheter position include the following: (a) the immediate appearance of His bundle deflections on termination of the tachycardia order 160 mg malegra dxt plus overnight delivery erectile dysfunction medications that cause, or conversely, disappearance of the His bundle deflection on initiation of the tachycardia, without catheter manipulation; (b) spontaneously occurring or induced supraventricular capture of the His–Purkinje system (with or without ventricular capture) during the tachycardia with the sudden appearance of His bundle deflections; and (c) in the presence of supraventricular capture, H-V intervals comparable to those during sinus rhythm (Figs. We have found that the use of more closely spaced bipolar electrodes (l to 5 mm apart) facilitate identification of His bundle activity when it occurs within the ventricular electrogram. The second atrial impulse (A) conducts through the His bundle but fails to alter the tachycardia. The first and third sinus complexes block in the A-V node due to retrograde concealment. Two complexes later, another supraventricular fusion is observed, again without influencing the tachycardia. This demonstrates lack of requirement of the His bundle for perpetuation of the tachycardia. If His deflections are not spontaneously observed during the tachycardia, because of either poor position or obscuration of the His deflection by the ventricular electrogram, rapid atrial pacing can be used to clarify the issue in some cases. Thus, knowledge of A-V conduction during sinus rhythm may be necessary to define what is a “normal” H-V interval during the tachycardia. Some investigators , suggest that the site of origin of such a tachycardia is within the His–Purkinje system. As stated earlier, pre-excited tachycardia using either an A-V or nodoventricular bypass tract must be excluded (see Chapter 10). It is not rare for a tachycardia to have a V-H interval less than the antegrade H-V interval (Fig. Retrograde conduction time over the His–Purkinje system is actually much greater than the “V-H” observed during the tachycardia. Depending on the relative conduction time up the His–Purkinje system and through slowly conducting P. Atrial pacing is begun (arrow) at a cycle length of 480 msec, which is gradually reduced to 400 msec. As the atrial-paced cycle length decreases, a greater degree of ventricular activation is produced via the normal conducting system. The His deflection typically occurs before the right bundle deflection with an H-V interval approximating the H-V interval during sinus rhythm. Theoretically, if there is prolonged retrograde conduction over the His–Purkinje system, producing a markedly delayed His deflection (very long V-H), the “in parallel” activation of the His bundle would appear as a “normal” H-V interval. In this case, one must demonstrate that the His deflection is not a requisite for subsequent ventricular activation and thus is not a reflection of bundle branch reentry. Certain criteria are necessary for the diagnosis of bundle branch reentry, all of which provide P. The mechanisms of bundle branch reentry and its variants are discussed in greater detail later in this chapter. B: The schema shows that propagation of the impulse from the reentrant circuit to the His–Purkinje system is more rapid than that to the remainder of the myocardium, resulting in a short V-H interval. In this instance, conduction to the His–Purkinje was far more rapid than that to the ventricular myocardium, resulting in early His–Purkinje activation. These differences make it mandatory that these arrhythmias not be lumped together in terms of response to stimulation, effects of pharmacologic therapy, effectiveness of ablation, and clinical outcome. Anatomic Substrate The most common anatomic substrate for all these arrhythmias is chronic coronary artery disease, usually associated with prior infarction. Arrhythmias that are due to coronary artery disease are the only ones for which we have a reasonable understanding of the pathophysiologic substrate required for their genesis. Although sustained uniform monomorphic tachycardia may occur in the presence of either hypertrophic or idiopathic dilated cardiomyopathy, or even in patients with normal hearts, it is relatively uncommon. In these instances, the pathophysiologic basis for the arrhythmia is not well understood although patchy or segmental fibrosis is a common denominator. Arrhythmogenic right ventricular dysplasia has similar pathology as infarction, but it starts on the epicardium and additionally has fatty infiltration of the myocardium. This may occur because in most cases there is patchy fibrosis instead of the large areas of contiguous scar seen in infarction. Regardless of the underlying cardiac pathophysiology, sustained monomorphic tachycardia can be studied electrophysiologically such that interpretation of the mechanism and development of therapy is possible. Electrophysiologic studies are most useful in patients with coronary artery disease and prior infarction. The pathologic substrate for patients with ventricular tachyarrhythmias associated with coronary artery disease is 20 21 22 23 usually a prior myocardial infarction resulting in wall motion abnormalities. The second group of patients who present with a cardiac arrest are those who have severe coronary artery disease and relatively normal ventricular function; in this group the arrest is most likely due to acute ischemia. Our patient population is clearly selected so that we study patients with lower ejection fractions, recognizing that lower ejection fraction per se places a person at high risk for sudden death. The extent of infarction, and perhaps location involving the septum, may be the two important prognostic factors associated with these 21 24 malignant sustained ventricular arrhythmias. The cycle lengths of the tachycardias occurring early after infarction, however, tend to be faster, and the tachycardia is more poorly tolerated. This may reflect evolving scar formation, which when ultimately completed, may be related to longer tachycardia cycle lengths, owing to abnormalities of conduction with which it is 26 associated (see following discussion). Thus, some components of the anatomic substrate must be relatively fixed once infarction has 27 occurred. This is supported by inducibility at 10 and 100 days in an Ovine infarction model. Moreover the ability of programmed stimulation to predict risk of sudden cardiac arrest and survival postinfarction lead credence to 28 this hypothesis. Attempts to make these correlations are fraught with selection and/or entry bias, which is inherent in selecting patients from catheterization laboratories, coronary care units, or exercise laboratories. Similarly, patients studied following cardiac arrest are a selected group of survivors, and as such may not reflect the timing from infarction to cardiac arrest of nonsurvivors. However, this may indicate some of the characteristics of those patients likely to survive. Of more than 1,100 selected survivors of cardiac arrest associated with coronary artery disease who we have studied, the highest incidence (≈50%) of cardiac arrest occurred in the first 6 to 12 months following infarction. After the first year following infarction, the incidence of cardiac arrest decreases rapidly, such that within 3 years the incidence is low. In the thrombolytic and primary angioplasty era, the timing of these events has not changed, but, as stated above, their frequency has been significantly reduced. The pathophysiologic substrate in disease states other than coronary artery disease is less clear. Electrophysiologic Substrate The clinically measurable electrophysiologic consequences of infarction that are potentially arrhythmogenic include abnormalities of conduction and refractoriness, heterogeneity of conduction and refractoriness, enhanced automaticity, and areas of inexcitability. Unipolar (top) and bipolar (bottom) signals recorded with the Rhythmia mapping system. The bipolar signal removes the large farfield signal recorded in the two unipolar electrograms from which the bipolar signal is derived. We developed criteria for normal, abnormal, and fractionated electrograms using bipolar signals recorded with a Bard Josephson catheter (see Fig. Normal electrograms had sharp, biphasic, or triphasic spikes with amplitudes of ≥3 mV, durations of ≤70 msec, and/or an amplitude/duration ratio of ≥0. We defined fractionated electrograms as abnormal electrograms that fell outside the 95% confidence limits of amplitude and duration of all abnormal electrograms. The most common abnormalities were low voltage and increase in electrogram duration, both of which appear to be nonspecific markers of infarction or even poor contact. Multicomponent and fractionated electrograms, isolated late potentials and late electrograms were more closely related to 31 arrhythmogenic sites; but the positive predictive value was only ∼30%. Only 14% of “sites of origin” came from sites that demonstrated normal electrograms. It should be obvious that since mapping catheters have different size electrode (tip and ring), normal and abnormal electrogram characteristics need to be defined for each catheter. Subsequent intraoperative studies using a 20 pole plaque electrode showed that successful surgery was associated with elimination of isolated late potentials and split potentials suggesting mechanistic significance 37 (Fig. The first two complexes are sinus in origin and the left ventricular recordings show markedly abnormal electrograms. Multiple components are present, and the electrogram exceeds 160 msec in duration. We defined total endocardial activation as the time from the earliest local activation to the time of the latest local activation. We used the total endocardial activation time, the duration of the longest electrogram recorded, the presence of late electrograms (including late potentials), and the extent of abnormal P. These abnormalities of activation, whether recorded endocardially in the catheterization laboratory or intraoperatively, occur only in areas of prior infarction and 35 36 38 39 significant wall motion abnormalities. Sites 2, 3, and 4 are the septum, 1 is the apex, 5 and 6 are the mid- and basal inferior wall, 8 is the inferoposterior wall, 9 is the apical anterolateral wall, 10 is the basal lateral wall, 11 is the midanterior wall, and 12 is the basal anterior wall. Endocardial catheter mapping in patients in sinus rhythm: relationship to underlying heart disease and ventricular arrhythmias. Three surface recordings accompanied by three local bipolar electrograms (normal, abnormal, and fractionated and late) recorded from different left ventricular endocardial sites are shown. The arrows show the onset and offset (characterized by the amplification signal decay artifact) of local electrical activity. Endocardial catheter mapping in patients in sinus rhythm: relationship to underlying heart disease and ventricular arrhythmias. Normal values and abnormal electrograms recorded with this plaque are shown on the left.

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The in- tioning of the individual’s immune appara- creased vascular permeability will allow tus purchase malegra dxt plus amex erectile dysfunction natural cures, either in producing antibody or creating easier access for neutrophils and mono- immune-competent cells for cell-mediated cytes buy malegra dxt plus 160 mg without a prescription erectile dysfunction home remedies. When the individual is facing the same antigen subsequently order malegra dxt plus 160 mg without a prescription erectile dysfunction drugs and glaucoma, there is no la- tent or lag phase and the immune response is prompt buy malegra dxt plus online now erectile dysfunction of diabetes, powerful and prolonged (Table 3. In contrast to the innate immune response, which recognize the common molecular Fig. They are: specific immune responses are intimately involved in igniting the specific immune 1. The antigenic specificity of the immune system permits it to distinguish minor differ- Naturally acquired active immunity: This type ence among antigens. The antibodies can of immunity is obtained when a person is ex- distinguish between two protein molecules posed to antigens in the course of daily life. The Once acquired, the immunity lasts for rest of immune system is capable of generating its life such as in measles and chickenpox. Once clinical infections can also conform immuni- the immune system recognized and respond- ty as that occurs in tuberculosis. Adults have ed to an antigen, it exhibits immunological natural immunity against polio after repeated memory to recognize the same antigen, sub- subclinical infections. Finally, the immune sys- eases, a special type of immunity is observed tem, normally responds to foreign antigens, known as infection immunity (premunition). Pertussis vaccine Bacterial capsule Passive Immunity polysaccharides Passive immunity is resistance exhibited by Haemophilus infu the host, when ready-made antibodies or enzae defensive cells are introduced into the body. Certain antibod- diphtheria tetanus ies (IgA) are passed from the mother to her Bacterial nursing infants in breast milk, especially in the first secretion called colostrum. The im- products munity in infants last as long as baby feeds and killed on breast milk. Viral vaccines nal antibodies are also transferred through Live and placenta to the fetus. Adoptive immunity is a special type of immu- Artificially acquired passive immunity: This nization, where the immunocompetent cells type of immunity involves the introduction are injected. These antibodies phocytes, an extract of lymphocytes (transfer come from animal or person, who is already factor of Lawrence) may be introduced as a immune to the disease. Hyperimmune sera of animal or human as lepromatous leprosy, immunodeficiency origin. Human gamma globulin is also used The mucosal immune system is composed of in the treatment of immunodeficiency the lymphoid tissues that are associated with diseases. Passive immunization may also be em- mucosal surface depends on both intact mu- ployed to suppress active immunity, cosal immue responses and non-immunolog- when the latter may be injurious. The ic protective functions such as residential bac- commonest example is the use of Rh im- terial flora, mucosal motor activity (peristalsis; munoglobulin during delivery to prevent ciliary function), mucus secretion that create immune response to rhesus factor in Rh- barrier between potential pathogens and epi- negative women with Rh-positive babies. At times, both active and passive immu- The concept local immunity has gained nization is given together. Ideally, it is em- importance in the treatment of infections, ployed to provide immediate protection to which are either localized or where it is op- non-immune individual with a tetanus-prone erative in combating infection at the site of wound. Microbiology: Principles and exhibited by a community, which is relevant Applications, 3rd edition; 1996. Melnick and Adelberg’s Medical fection could spread rapidly through the Microbiology, 25th edition. Basic and Clinical forms might arise that could evade the im- Immunology, 1st edition; 1997. As a rule, the immune response is carried out by cules or even degraded fragments of antigen. Based upon the nature of immune respons- The recognition of antigen by T cells and es they generate, the antigens/epitopes are di- B cells is fundamentally different. B cells vided into three broad functional categories: recognize soluble antigen when it binds to 1. In the context of this ex- antibody or sensitized lymphocytes, which planation, the antigen can be defined as the in turn react specifically with immunogens, substance that can be recognized by the Ig, which produced them. Some small mole- (pneumococcal polysaccharide, bacte- cules called haptens are antigenic, but in- rial lipopolysaccharide, fimbrial and fla- capable by themselves of inducing specific gellar antigen) (Fig. Haptens (partial Antigens) T-dependent Antigens Haptens are small molecular weight sub- stances, which are antigenic, but incapable Do not stimulate antibody production by themselves of inducing specific immune without the help of T lymphocytes, e. In these people, when penicil- lin combines with serum protein, the result- Antigens vary widely in degree to which they ing combined molecules initiate an immune are immunogenic. Tolerogens Molecular Weight Tolerogens are antigens (usually self), which The most potent immunogens are usually induce in normal condition, immune unre- large proteins. They be- come immunogenic only when linked to immune response against the self-tissue in carrier protein. Lipid and nucleic acid are less im- Based on origin, antigens are classified into munogenic than heteropolymer containing following types. In Somatic gelatin, there are no aromatic amino acids Flagellar such as tyrosine. These lipid- gens with regularly repeating epitopes presenting molecules are members of cluster Antigen 37 Fig. However, when the hapten is combined with a larger carrier molecule, usually a serum protein, the hapten and its carrier together function as an antigen and can stimulate an immune response. Recognition of susceptibility to Tissue Enzymes lipid by T cells, as a part of immune response Substances, which are metabolized and are to some pathogens (Mycobacterium tubercu- susceptible to enzymic action, are antigenic losis, M. An important function of the immune sys- tem is to distinguish self (host) from non-self Dosage, Route and (foreign). Therefore, the more dissimilar a Timing of Antigen molecule from host molecules, the greater Administration also determine the immuno- its immunogenicity. It is possible to enhance the immu- nogenicity of a substance by mixing it with Antigenic Determinants (Epitopes) an adjuvant. Adjuvants are substances that An antigen may have one or more antigen- maintain the continuous stimulation of the ic determinants (a determinant is roughly immune responsive cells by slow release. On the other hand because of a different composition of im- the innate immune system uses preformed mune response genes. Using hapten (atoxyl) coupled with protein, it was seen that antigenic specificity is determined by a single chemical grouping even by a single acid radical. The importance of position (ortho, meta and para) of the an- tigenic determinants in antigen molecules is Fig. An- antigens have repeating units that can cross-link several antigen receptors on the same B cell. Cross reac- antigens stimulate the B cell to make antibodies tion can occur between related species. The polysaccha- The specificity of natural tissue antigens rides of bacterial capsules are examples for this type of animals may be of various types: of antigen. These isoantigens, paralytic complication following neural an- besides being of clinical importance in blood tirabies (sheep brain) vaccine is the result of transfusion and isoimmunization in pregnan- cross reaction of organ-specific antigens. The same or closely related antigens may occur in different biological species, classes Histocompatibility antigens are those cel- and kingdom. These antigens are known as lular determinants specific for each individ- heterogenetic or heterophile antigens. These are recognized by geneti- of the examples of heterophile antigen is cally different individual of the same species; Forssman antigen. This is a lipid-carbohy- when attempts are made to transfer or trans- drate complex widely distributed in human plant cellular material from one individual to beings, animals, birds, plants and bacteria. Histocompatibility antigens are associ- Other heterophilic antigens, used in serolog- ated with plasma membrane of tissue cells. The used as antigens in the diagnosis of ty- major histocompatibility antigens determin- phus fever (Weil-Felix). Red cell antigen in the diagnosis of pri- Autospecificity mary atypical pneumonia caused by Autologous or self-antigens are ordinarily Mycoplasma pneumoniae (cold aggluti- non-antigenic, but in certain circumstances nation test). When these antigens are released into Essay Questions the circulation (by injury to lens or damage 1. Define antigen, discuss about the deter- to the testis) antibodies are produced against minants of antigenicity. Antigen Recognition Molecules 5 In order for the immune system to respond All the above stated molecules have to non-self, i. They have a system capable of precisely distinguishing domain structure built on three dimensional self from non-self has to evolve. What are the features known as immunoglobulin fold (Ig molecules, which recognize and bind to an- fold). Antibodies [immunoglobulins (Ig)], which family known as Ig supergene family (Fig. Ig satisfies the structural and chemical con- Tiselius, in 1937 separated serum pro- cept, the antibody provides biological and teins by electrophoresis into albumin, alpha- functional concept. All antibodies are Ig, but globulin, beta-globulin and gamma-glob- all Ig are not antibodies. Antibody activity was associated with Immunoglobulins constitute 20% to 25% gamma-globulin. Based on the physi- Sedimentation studies using ultracentri- cochemical, antigenic differences and the fuge disclosed the diversity of the antibody types of heavy chain Igs are classified into molecules. Light (L) chains Thus, indiscriminate use of various termi- are of one of the two, kappa (K) or lambda nologies led to confusion. Both types can occur in all classes of Ig mon terminology was evolved called Ig and (IgG, IgM, IgA, IgE and IgD), but any one Ig was accepted internationally.