One of the classic and best-characterized examples of innate immunity is the activation of interferon signaling that occurs with viral infection generic super levitra 80 mg overnight delivery erectile dysfunction after stopping zoloft. Both types of interferons are effective at limiting 36 viral replication when added to infected cells or when administered to a coxsackievirus-infected mouse order super levitra 80mg line erectile dysfunction pills herbal. The absence of type I interferon receptors or interferon-β in mice is associated with a marked increase in mortality rates but has less effect on early viral replication in the heart. Additional content on this this topic is discussed in an online supplement for this chapter titled The Role of Innate Immunity in Myocarditis. The receptors recognize pathogen-associated molecular patterns activating a defense against the invading pathogens. Other Innate Immune Mechanisms Other innate immune responses are important in the control of the initial phases of viral infection. Activation of inflammasomes has been demonstrated to occur in patients with acute viral myocarditis within the first 4 weeks of the onset of the disease. The inflammasome is a macromolecular complex that is activated during myocardial injury. It is thought that inflammasome activation can limit viral replication, though it could also damage the cell. Evasion of the inflammasome process might 5,6 decrease myocardial cell damage, but might also contribute to viral persistence. Macrophages have been shown to have an important role in the early innate immune response. They act as scavengers, microbicidal effector cells, and regulatory cells in the onset of cardiac inflammation. Early hi recruitment of inflammatory macrophages (Ly6C ) occurs following cardiac injury. Although macrophages are involved in the early response to injury, they are also responsive to T cells. The interferon-γ secreted by Th1 cells potentiates low microbicidal activity of macrophages. Ly6C M2 macrophages blunt the inflammatory response and 7 predominate during myocardial healing. Acquired Immunity Acquired immunity becomes a prominent manifestation of viral myocarditis beginning approximately 4 to 5 days after the viral infection, although the peak and pattern of activation are variable. The acquired immune response is an antigen-specific response that is directed to a single antigen and is mediated by T and B cells. T cells are targeted to infected cells and attempt to limit infection by destroying the host cell through secretion of cytokines or perforins. These can contribute to the death of the infected cell through necrotic and/or apoptotic mechanisms. Thus, although T cell–mediated immune mechanisms are important for controlling and limiting viral replication, they also can have detrimental effects on the infected organ by stimulating cell death mechanisms in the infected host. Appropriately limiting the T-cell and B-cell immune mechanisms could limit damage to the heart, but such inhibition needs to be balanced by the need 40 to inhibit viral replication. The acquired immune process is initiated when the variable region of the T-cell receptor binds to + peptides with specific amino acid sequences that are recognized as foreign to the host. Cytokines in the cellular microenvironment can control how the cells differentiate. The precise cellular signaling cascades and pattern of cytokine production that are associated with 40,41 differentiation of these distinct T-cell subtypes has been reviewed elsewhere. Appropriate regulation of effector T cells is needed to control infections and at the same time avoid inappropriate immunologic destruction of host tissue such as myocardial cells. Activation of T cells also leads to B-cell activation, which results in secretion of antigen-specific antibodies directed against the invading pathogen. After initial activation, the immune cells undergo clonal expansion to attack the source of antigen, which could include a viral coat protein or, in some cases, proteins in the cardiac myocyte such as myosin. There is evidence that cross reaction with the host may occur because of “molecular mimicry” between the virus and the host. Treg cells have important functions for the suppression of Th1-cell and Th2-cell immune responses and were previously identified as T helper cells. The activation of T cells is highly dependent on an interaction with the innate immune-signaling cascade. When p56lck is genetically deleted from the mouse, typical myocarditis is almost eliminated, with no significant mortality rates after 42 infection. Alterations in any of the pathogenic mechanisms just described could, theoretically, affect the susceptibility to viral infection. For example, alterations in the mechanism of viral entry and replication, innate or acquired immune-signaling mechanisms, or the integrity of the sarcolemmal membrane could affect the susceptibility to develop myocarditis on exposure to a given virus. Nutrition is also likely to have an effect on the susceptibility to viral infection. It is thought that a deficiency of selenium can increase the risk of myocarditis, as has been described in the Keshan province in China. Furthermore, selenium deficiency in mice also increased the susceptibility to enteroviral myocarditis. The number of mechanisms known to affect the susceptibility to myocarditis in humans is far from complete. The virus can directly enter the endothelial cells and myocytes and effect changes that lead to direct cell death or hypertrophy. The inflammatory process outlined earlier for both innate and acquired immunity can lead to cytokine release and activation of matrix metalloproteinases that digest the interstitial collagen and elastin framework of the heart (see Chapter 23). Clinical Syndromes Myocarditis has a wide-ranging array of potential clinical presentations, a feature that contributes to the difficulties in diagnosis and classification. The clinical picture may be one of asymptomatic electrocardiographic or echocardiographic abnormalities or may include signs and symptoms of chest pain, cardiac dysfunction, arrhythmias or heart failure, and/or hemodynamic collapse. Transient electrocardiographic or echocardiographic abnormalities have been observed frequently during community viral outbreaks or influenza epidemics, but most patients remain asymptomatic from a cardiac standpoint and have few long-term sequelae. Coronary vasospasm, demonstrated using intracoronary acetylcholine infusion, is one cause for chest pain in patients with 43 clinical signs of myocarditis in the absence of significant coronary atherosclerosis. Chest pain also may mimic that in pericarditis, suggesting epicardial inflammation with adjacent pericardial involvement. The outcome of myopericarditis generally is good, with only two sudden deaths reported from four published case series (N = 128) (Table 79. Additional content on clinical syndromes is presented in an online supplement for this chapter entitled Specific Clinical Presentations of Myocarditis. Myocarditis typically has a bimodal distribution in terms of age in the population, with the acute or fulminant presentation more commonly seen in young children and teenagers. The difference in presentation probably is related to the maturity of the immune system, whereby the young tend to mount an exuberant response to the initial exposure of a provocative antigen. By contrast, older persons would have developed a greater degree of tolerance and show a chronic inflammatory response only to the chronic presence of a foreign antigen or with a dysregulated immune system that predisposes to autoimmunity. Viral myocarditis has 44 been associated with heart failure from both systolic and isolated diastolic dysfunction. Associated physical examination findings point to specific causes for myocarditis.
It may bear some resemblance to the verruca vulgaris (which can occur in the nasal cavity) generic super levitra 80mg online erectile dysfunction doctor denver, but on histopathologic examination buy cheap super levitra online impotence over 50, it is an exophytic lesion with a non-keratinized surface that includes mucous cells and transitional epithelium. The oncocytic papilloma may combine exophytic and endophytic growth patterns, but the epithelium is distinctive. It is composed of mitochondria-rich oncocytes that are tall, columnar, and sometimes ciliated. Neutrophilic microabscesses and mucin cysts may also be present in the epithelium. Care should be taken to remove all of the lesions during the ﬁrst surgery in order to minimize the risk of recurrence. Speciﬁc surgical techniques can be employed based on the extent and location of the lesions (Anari and Carrie 2010). Recurrence is a major concern, but precise rates are difﬁcult to determine and vary widely (Mirza et al. Most recurrences appear in the ﬁrst 2–3 years after initial surgical treatment with an incidence of 5–50 % depending on the amount of disease and adequacy of initial tumor removal (Anari and Carrie 2010; Mirza et al. Vigilant postoperative surveillance is recommended to detect any early recurrence. These entities are very rare, and, with the possible exception of epidermodysplasia verruciformis, there is a dearth of infor- mation regarding their pathogenesis. The primary concern is malignant transformation, usually occurring on sun-exposed areas of the skin in about half of affected individuals beginning in the fourth or ﬁfth decade of life (Rogers et al. Benign lesions exhibit irregular distribution of keratohyaline granules in the upper levels of the epithelium along with clear changes in suprabasal cells. When malignant transformation occurs, these somewhat distinctive changes are lost, and the microscopic appearance is Bowenoid, with marked dyskeratosis and pleomor- phism (Majewski and Jablonska 1997). There are case reports of Netherton syndrome patients with papillomatous skin lesions and cutaneous malignancies (Folster-Holst et al. It is a migratory annular skin rash, with a “serpiginous overlying double- edged scale” (Sun and Linden 2006). The “bamboo hair” of Netherton patients is often thin and fragile, breaking within a few centimeters of the scalp. This is a necessary ﬁnding for the diagnosis of Netherton syndrome (Sun and Linden 2006). Many Netherton patients also experience an atopic diathesis with allergic rhinitis, asthma, angioedema, dermatitis, and other manifestations (Sun and Linden 2006). In addition to the three major clinical signs previously mentioned, non- cutaneous ﬁndings such as physical and mental retardation, chronic enteropathy with failure to thrive, recurrent infections, aminoaciduria, and anaphylactoid reactions to certain foods have been described (Folster-Holst¨ et al. The epidermis is usually psoriasiform, “with acanthosis, hypergranulosis, and occasionally, spongiosis progressing to microvesiculation” (Sun and Linden 2006). Trichorrhexis invaginata is especially distinctive under light microscopy, with torsion and invagination nodules that may exhibit intussusception of the proximal nodule over the distal (Sun and Linden 2006) 156 S. Recurrent infections should be treated with antimicrobials directed at the cultured organisms. Approximately 79 % of them initially presented with warts, 90 % with hypogammaglobulinemia, and 92 % with neutropenia (Kawai and Malech 2009). They noted that all patients from early childhood suffered from a wide variety of recurrent bacterial infections due to neutropenia, B cell lymphopenia, and hypogammaglobulinemia (Kawai and Malech 2009). If this is accompanied by neutrope- nia, lymphopenia, and hypogammaglobulinemia, a biopsy should be performed. Mortality and morbidity due to infection is apparently low in closely-followed patients, but premature death due to overwhelming infections and carcinomas has been reported (Kawai and Malech 2009). The potential for wide- spread lesions appears to be increased in patients with immunodeﬁciencies. Arch Dermatol Res 279 Suppl:S66–72 Ritzkowsky A, Weissenborn S, Krieg T, Pﬁster H, Wieland U (2001) Extensive human papillo- mavirus type 7-associated orofacial warts in an immunocompetent patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102: 431–432 Henquet C (2011) Anogenital malignancies and pre-malignancies. Surv Ophthalmol 49:3–24 Sen S, Sharma A, Panda A (2007) Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: a retrospective study. Indian J Ophthalmol 55:361–363 Hall C, McCullogh M, Angel C, Manton D (2010) Multifocal epithelial hyperplasia: a case report of a family of Somalian descent living in Australia. Mod Pathol 15:279–297 Eggers G, Muhling¨ J, Hassfeld S (2007) Inverted papilloma of paranasal sinuses. J Craniomaxillofac Surg 35:21–29 Anari S, Carrie S (2010) Sinonasal inverted papilloma: narrative review. Otolaryngol Clin North Am 39:619–37, x–xi Sauter A, Matharu R, Hormann¨ K, Naim R (2007) Current advances in the basic research and clinical management of sinonasal inverted papilloma (review). J Am Acad Dermatol 60:315–320 Gewirtzman A, Bartlett B, Tyring S (2008) Epidermodysplasia verruciformis and human papil- loma virus. South Med J 96:613–615 Majewski S, Jablonska S (1997) Human papillomavirus-associated tumors of the skin and mucosa. Int J Dermatol 45:693–697 Folster-Holst R, Swensson O, Stockﬂeth E, Monig H, Mrowietz U, Christophers E (1999) Comel-¨ ¨ ` Netherton syndrome complicated by papillomatous skin lesions containing human papillomaviruses 51 and 52 and plane warts containing human papillomavirus 16. Arch Dermatol 146:69–73 Yanagi T, Shibaki A, Tsuji-Abe Y, Yokota K, Shimizu H (2006) Epidermodysplasia verruciformis and generalized verrucosis: the same disease? Clin Exp Dermatol 31:390–393 M alignant Diseases Associated with Human Papillomavirus Infection Herve Y. For each site, the epidemiology, clinical features, diagnosis, treatment, and prognosis are examined. This is supported by scientiﬁc research that was conducted decades ago (Reid et al. Cervical cancer is believed to evolve from cervical dysplastic lesions of escalating grades (Leung et al. Types 16 and 18 are generally acknowledged to cause about 70 % of cervical cancer cases. Preventive programs of repeated Malignant Diseases Associated with Human Papillomavirus Infection 165 cytological examination screening (Papanicolaou test, commonly known as the Pap test) have been credited with reducing cervical cancer mortality by more than 50 % (Shield et al. Human papillomavirus types 16 and/or 18 prevalence world- wide in women with normal cervical tissues at screening is estimated by the World Health Organization at 3. There is evidence that in North America, progression to invasive disease is often because of a lack of screening rather than screening failure (Spayne et al. More advanced disease is often addressed with removal of the cervix, cervix and uterus (hysterectomy), radiation therapy and/or chemotherapy (usually cisplatin). A Cochrane review suggested that the addition of chemotherapy and radiotherapy may be beneﬁcial in some cases (Rosa et al.
All patients undergoing splenectomy should receive polyvalent pneumococcal and Haemophilus influenza vaccines generic super levitra 80mg line erectile dysfunction injection. Anatomic relation of the spleen to the liver super levitra 80 mg sale erectile dysfunction pills made in china, diaphragm, pancreas, colon, and kidney. This may be accomplished by the use of local hemostatic techniques (electrocoagulation, argon beam coagulator, Surgicel or Gelfoam soaked in thrombin, microfibrillar collagen, and the use of fine sutures or mattress sutures with Teflon felt pledgets). Recently, splenectomy has been performed laparoscopically if the spleen is near normal size (see Laparoscopic Splenectomy, p. They are usually approached through a long midline incision for adequate exposure and to assess their resectability. Resection of such lesions may require excision of adjacent or involved small bowel or large intestine or other involved abdominal viscera. Care must be taken not to injure the ureters or major vessels, particularly at the root of the mesentery to the small bowel. In certain tumors, the patient may still benefit from “tumor debulking” (removing as much tumor as possible and treating the remaining tumor with radiation and/or chemotherapy). Although most operative approaches are transabdominal, some retroperitoneal tumors may be approached retroperitoneally via oblique incision on either side of the abdomen. It is important to know the anatomy of these spaces for making a correct diagnosis and for treatment. Most commonly abscesses are drained by interventional radiology (85%), but some may require an open surgical approach. After the abscess is localized, the cavity is entered by finger dissection and drained. Variant procedure or approaches: Percutaneous approaches have become more popular as experience is gained by interventional radiologists. This technique should be reserved for unilocular collections, where sterile cavities are not penetrated and a safe route is available. Direct hernias are medial to the inferior epigastric artery and vein, whereas indirect hernias are lateral to these vessels. In general, an anterior approach (Bassini, McVay’s, Shouldice, or mesh repair) is used for primary repair of an indirect or direct inguinal hernia. The Bassini repair consists of ligation of the hernia sac and suturing the conjoint tendon to the shelving edge of Poupart’s ligament. McVay’s repair sutures the conjoint tendon to Cooper’s ligament and usually is reserved for femoral inguinal hernias. Shouldice emphasizes the closing of the transverse fascia and transversus abdominal muscle layers. Currently, the interposing of Marlex mesh or insertion of a Marlex plug between the conjoint tendon, the internal oblique muscle, and the inguinal ligament is commonly used. T h e posterior preperitoneal approach is normally performed by suturing the transversus abdominis arch on the superior aspect of the hernia defect to Cooper’s ligament and the iliopubic tract on the inferior aspect of the defect. The laparoscopic approach is indicated for the repair of recurrent or bilateral inguinal hernias and utilizes a preperitoneal patch repair and results in less postop pain and an earlier return to normal physical activity (see Laparoscopic Inguinal Hernia Repair, p. Hallen M, Bergenfelz A, Westerdahl J: Laparoscopic extraperitoneal inguinal hernia repair versus open mesh repair: long-term follow-up of a randomized control trial. Neumayer L, Giobbie-Hurden A, Jonasson O, et al: Open mesh versus laparoscopic mesh repair of inguinal hernia. If the hernia cannot be reduced, the possibility of strangulation needs to be kept in mind. The peritoneal sac in most cases should be opened proximal to the femoral canal to gain control of the intestine before it reduces itself into the peritoneal cavity. The repair consists of suturing the iliopubic tract to Cooper’s ligament, taking care not to compromise the femoral vein (McVay repair). Factors leading to herniation are wound infection, trauma, inadequate suturing, and ischemia. Following skin incision, the skin edges and subcutaneous fat are retracted and the dissection is carried down to the hernia defect. The redundant hernia sac is excised and the fascia is freed up on both sides of the wound. Variant procedure or approaches: In addition to primary repair, the latter may be reinforced by an onlay mesh prosthesis, or the prosthesis may be used to fill the hernial defect or placed behind the muscle layer. In the repair of incisional hernias, laparoscopic tacking of mesh is gaining in popularity. A complete dehiscence is a separation of all layers of the abdominal wall and often is associated with an extrusion of abdominal viscera. If incomplete, the separation of fascial and muscular layers results in an incisional hernia or an obstruction of a herniated loop of intestine. The earliest sign of a wound dehiscence is the presence of serosanguineous drainage from the wound. Minimal disruptions may be treated conservatively with occlusive dressings and an abdominal binder. Major dehiscence requires operative repair using careful fascial closure and retention sutures. Variant procedure or approaches: Variations in the type of closure depend on surgeon’s preference. The patient population may range from premature infants to the elderly, who have the potential for presenting with multiple medical problems. Choice depends on factors such as site of incision, patient physical status, and preference of both patient and surgeon. Palpable lesions include masses, nodules, or areas of asymmetric breast thickening. Breast pathology can manifest as skin changes —specifically, edema, redness, brawny discoloration, or ulceration—mandating biopsy of the involved skin and underlying breast tissue. The term excisional biopsy is usually applied to benign entities and implies the complete removal of the lesion in question (e. The term lumpectomy is used to characterize cancerous lesions that are removed with a rim of normal breast tissue to achieve tumor-free margins. Another reason for excisional biopsy is the occurrence of bloody or pathological nipple discharge. The underlying cause of this abnormality is, in most instances, a benign intraductal papilloma or, infrequently, carcinoma. Ductoscopy may be used to explore breast ducts that produce abnormal discharge fluid. It is inserted into the duct(s) following progressive dilatation with lacrimal probes. After the intraductal lesion is visually identified, the surgeon injects methylene blue to further guide the duct excision and breast biopsy.
For example generic super levitra 80 mg with visa what is an erectile dysfunction pump, such incomplete recovery is the usual mechanism responsible for a nonconducted premature P wave or one that conducts with a functional bundle branch block buy super levitra with visa erectile dysfunction pump operation. Correctly used, decremental conduction refers to a situation in which the properties of the fiber change along its length such that the action potential loses its efficacy as a stimulus to excite the fiber ahead of it. Thus the stimulating efficacy of the propagating action potential diminishes progressively, possibly as a result of its decreasing amplitude and slowed upstroke velocity. Reentry Electrical activity during each normal cardiac cycle begins in the sinoatrial node and continues until the entire heart has been activated. Each cell becomes activated in turn, and the cardiac impulse dies out when all fibers have been discharged and are completely refractory. If, however, a group of fibers not activated during the initial wave of depolarization recovers excitability in time to be reactivated before the impulse dies out, the fibers may serve as a link to reexcite areas that were just discharged and have now recovered from the initial depolarization. Such a process has been given various names—reentry, reentrant excitation, circus movement, reciprocal or echo beat, and reciprocating tachycardia—and all have approximately the same meaning. Entrainment represents capture or continuous resetting of the tachycardia by the pacing-induced activation. Each pacing stimulus creates a wavefront that travels in an anterograde direction (orthodromic) and resets the tachycardia to the pacing rate. A wavefront propagating retrogradely in the opposite direction (antidromic) collides with the orthodromic wavefront of the previous beat. These wavefront interactions create electrocardiographic and electrophysiologic features that can be explained only by reentry. Therefore the criteria of entrainment can be used to prove the reentrant mechanism of a clinical tachycardia and form the basis for localizing the pathway traveled by the tachycardia wavefront. Map recording of B, C, and D also shows a progression of fusion, with both the morphology and timing of a portion of the electrogram changing with faster pacing. The black arrowhead indicates entry of the pacing impulse into the reentrant circuit, where it is conducted orthodromically (Ortho) and antidromically (Anti). However, the orthodromic wavefront from the pacing impulse (X) continues the tachycardia and resets it to the pacing rate. Right, Introduction of the next pacing impulse (X + 1) during rapid pacing from the same high atrial site. The black arrowhead again indicates entry of the pacing impulse into the reentrant circuit, where it is conducted orthodromically and antidromically. Once again, the antidromic wavefront from the pacing impulse (X + 1) collides with the orthodromic wavefront of the previous beat. In this case, it is the orthodromic wavefront of the previous paced beat (X), and an atrial fusion beat results. The orthodromic wavefront from the pacing impulse (X + 1) continues the tachycardia and resets it to the pacing rate. In all three parts, arrows indicate the direction of spread of the impulses; the serpentine line indicates slow conduction through a presumed area of slow conduction (stippled region) in the reentrant circuit. If conduction in this alternative route is sufficiently depressed, the slowly propagating impulse excites tissue beyond the blocked pathway and returns in the reverse direction along the pathway initially blocked, to reexcite tissue proximal to the site of block (Fig. A clinical arrhythmia caused by anatomic reentry is most likely to have a monomorphic contour (Video 34. Pictures of the optical activation maps of A stimuli obtained from three different experiments at2 A coupling intervals of 190, 220, and 190 milliseconds, respectively, were merged with the pictures of the2 mapping area to show the initiation of echo beats in A (Slow/Fast), C (Fast/Slow), and E (Slow/Slow) circuits. The numbers on the maps indicate the activation times in reference to the A stimulus. The 2 black arrow indicates anterograde conduction, and the asterisk and the dashed red arrow represent the site of earliest retrograde atrial activation. Mechanisms underlying atrioventricular nodal conduction and the reentrant circuit of atrioventricular nodal reentrant tachycardia using optical mapping. Stated another way, continuous reentry requires the anatomic length of the circuit traveled to equal or exceed the reentrant wavelength (λ). The latter, λ, is equal to the mean conduction velocity of the impulse multiplied by the longest refractory period of the elements in the circuit. Both values can be different at different points along the reentry pathway, and thus a tachycardia does not have a single wavelength. Conditions that depress conduction velocity or abbreviate the refractory period promote the development of reentry in this model, whereas prolonging refractoriness and speeding conduction velocity can hinder it. However, under certain conditions, conduction velocity in ventricular muscle and Purkinje fibers can be very slow (0. Such reentry frequently exhibits an excitable gap, that is, a time interval between the end of refractoriness from one cycle and the beginning of depolarization in the next, when tissue in the circuit is excitable. This condition results because the wavelength of the reentrant circuit is less than the length of the pathway. Electrical stimulation during this period can invade the reentrant circuit and reset its timing or terminate the tachycardia. Although “microanatomic” reentry (confinement of the reentrant circuit to a few adjacent myocytes) has been postulated to occur in fibrotic myocardium, its occurrence in intact heart muscle has not been demonstrated directly. This difficulty results from the inability unambiguously to distinguish microreentry from triggered activity with currently available techniques. In reentrant circuits with an excitable gap, conduction velocity determines the revolution time of the impulse around the circuit and therefore the rate of the tachycardia. Prolongation of refractoriness, unless it is long enough to eliminate the excitable gap and make the impulse propagate in relatively refractory tissue, does not influence the revolution time around the circuit or the rate of the tachycardia. Following V , the atria are excited retrogradely (A′) beginning in the distal coronary sinus, followed by atrial2 activation in leads recording from the proximal coronary sinus, His bundle, and high right atrium. A supraventricular tachycardia is initiated at a cycle length of 330 milliseconds. Dispersion of excitability, refractoriness, or both, as well as anisotropic distributions of intercellular resistance, permit initiation and maintenance of reentry. Functional heterogeneities in the electrophysiologic properties of the myocardium have been shown to contribute to the generation and maintenance of tachycardia and fibrillation. They can also change dynamically, as in an acutely ischemic myocardium or in the presence of repolarization-prolonging 1,49 agents. A very important determinant of the dynamically induced component of heterogeneity has been identified as electrical restitution, or variation of the action potential duration and conduction velocity with the diastolic interval. C, D, Spiral wave behavior several seconds after initiating a rotor in homogeneous two-dimensional tissue. Atrial Flutter Reentry is the most likely cause of the usual form of atrial flutter, with the reentrant circuit being confined to the right atrium in typical atrial flutter, where it usually travels counterclockwise in a caudocranial direction in the interatrial septum and in a craniocaudal direction in the right atrial free wall. This area of slow conduction is rather constant and represents the site of successful ablation of typical atrial flutter. Different reentrant circuits exist in patients with other types of atrial flutter, such as those that occur after surgery or ablation or that are associated with an atrial septal defect (see Chapter 75). They wander randomly throughout the atrium and give rise to new wavelets that collide with each other and are mutually annihilated or that give rise to new wavelets in a perpetual activity. The cycle length of the source in the left atrium determines the dominant peak in the frequency spectra. The underlying periodicity may stem from a repetitive focal source of activity propagated from an individual pulmonary vein or left atrial site to the remainder of the atrium as fibrillating waves.
Two cotton-tip swabs soaked with material from the vaginal pool should be air dried and placed in card- board boxes (not test tubes) super levitra 80 mg with visa erectile dysfunction acupuncture. Any apparent seminal stains on the skin of the victim should be recovered with saline-moistened pieces of cloth buy cheap super levitra impotence herbal medicine. Oral and rectal smears and swabs should also be obtained and retained in all autopsy cases. The slides should be placed either in clean plastic slide holders or in new cardboard holders. The latter should not be reused to prevent carryover of vaginal or seminal material to a subsequent slide placed in the cardboard container. Vaginal, rectal and oral slides should be stained in an attempt to identify any spermatozoa. When no sperm are observed, part of each of the swabs from the vagina, rectum, and mouth can be used for presumptive tests for acid phosphatase. If, however, sexual intercourse is still strongly suspected, or if the acid phosphatase test was weakly positive or questionable, an assay for semen-speciﬁc protein P30 should be performed. In the latter case, it is probable that the sperm was obtained from cervical mucus. Thus, it is important when searching for motile sperm in an individual alleged to have been raped only a few hours before to obtain this material from the vaginal pool and not from the cervix. Non-motile sperm with tails in the living individual are usually seen up to 26 h, with occasional reports of 2 to 3 days. The identiﬁcation of only a single sperm on one or two slides should make the examiner wary that he may have one of those cases in which there is unusual prolonged survival of the sperm, that is, sperm from cervical mucus. The presence of several sperm on a slide, with a history of the last voluntary intercourse 2 or 3 days before, would be inconsistent with the sperm’s originating at that time, but would be consistent with a recent rape. Rape 443 The survival time of spermatozoa in the vagina of living individuals as reported in the medical literature is quite variable. This can be explained by two factors: where the sample was collected, and what criteria are used to identify sperm. Swabs should be taken from the vaginal pool and not the cervix, because sperm can survive in cervical mucus much longer than in the vagina. Thus, sperm seen on a cervical swab may not be caused by the rape but by sexual intercourse 2 to 3 days before. Some clinicians identify sperm only when they see a complete spermatozoa — one with a head and tail. This difference in criteria of identiﬁcation explains some of the differences in reports of the persistence of sperm. The best study of the persistence of sperm in the vagina of living indi- viduals is by Willott and Allard. They found that it was rare to ﬁnd sperm with tails, especially after more than 6 h. Sperm heads were identiﬁed on an anal swab 45 h after intercourse and on a rectal swab 65 h after intercourse. A number of points should be remembered about the identiﬁcation of sperm in vaginal, rectal, and oral swabs. In addition, the times previously quoted for per- sistence of sperm are for living individuals. Sperm have been identiﬁed in the vagina of dead individuals 1 to 2 weeks after death. In dead individuals, the sperm are destroyed by decomposition, not drainage or the action of the vaginal secretions or cells. Sperm that is deposited on material like cotton, cloth, or paper and air dried can be identiﬁed years after the event. This could be caused by use of a condom, failure to ejaculate, drainage of semen or aspermia secondary to disease or a vasectomy. Because of this problem, substances were looked for in semen besides sperm that could be identiﬁed by biochemical means to indicate recent intercourse. The highest levels are within the ﬁrst 12 h, with gradual disappearance by 48–72 h. Because it usually disappears in the ﬁrst 24 h after intercourse, it is most useful as an indicator of recent intercourse, compared with non-motile sperm, which can be identiﬁed up to 2–3 days after intercourse. Thus, of 27 females allegedly raped in which acid phosphatase was negative, 26% were positive for P30, thus indicating sexual intercourse had taken place. A number of individuals have been positively identiﬁed and convicted on the basis of bite marks. The bite mark should then be documented photographically, with a scale present in the picture. If a forensic odontologist is on call, he should be summoned at the time of the examination to perform the aforementioned steps as well as taking a cast. If a suspect is arrested, a court order can be obtained to get an impression of his teeth to be compared with the injuries on the victim. Homosexual Rape For completeness, we should mention the victims of homosexual rape. Essen- tially the same procedures as those performed on the female rape victim should be performed on the male. The length, constitution, and number of the repetitive sequences are different for each person. If these match, and the test is done with sufﬁcient probes, there is virtually no doubt that the suspect is the source of the tissue to the exclusion of all other indi- viduals, except for an identical twin. This is possible if the second individual is a monozy- gotic twin, or because an insufﬁcient number of tests were per- formed to differentiate the suspect from the other individual. To determine this, the fre- quency of occurrence of selected alleles in the major population groups is determined, and testing is performed to determine the presence of these selected alleles. If the second allele tested for also occurs and this matches, then 99 out of 100 people are excluded. If sufﬁcient alleles are tested for, the probabilities for exclusion go into the millions or even billions. All nucleated cells in the body contain 23 pairs of chromosomes except for sperm and ova, which contain 23 chromosomes rather than 23 pairs. The sides of the ladder consist of alternating sugar (deoxyribose) and phosphate molecules; the rungs of the ladder consist of nitrogen bases. The weakest part of the helix or ladder is the rungs, where the nitrogen bases are weakly linked by hydrogen bonds. Two of these are purines (adenine and guanine) and two are pyrimidines (thymine and cytosine). In forming the rungs of the ladder, guanine always binds to cytosine and adenine always binds to thymine. These are the only two possible combinations and these are called complementary base pairs. Because of the millions of nucleotides forming a single strand and the fact 448 Forensic Pathology that there are 23 pairs of chromosomes in each cell, there is an almost inﬁnite variety in the arrangement of the nucleotides. A gene is a series of these bases that occupies a speciﬁc location (locus) on a chromosome, producing a speciﬁc product.
However discount super levitra 80 mg line erectile dysfunction groups, many foods with evidence for cardiometabolic benefits cheap super levitra 80mg without a prescription erectile dysfunction performance anxiety, including berries, nuts, and extra-virgin olive oil, are rich in phenolics, and their physiologic and molecular effects are highly promising for further study. Energy Balance In most countries, the current obesity epidemic is a striking change from decades of relative stability; in 196 the United States, obesity began steeply rising only about 35 years ago. Abdominal adiposity, which produces the greatest metabolic harms, has also increased more than overall weight in many nations, 197 especially in younger women. The breadth, depth, and pace of this epidemic, including in young 198 children, suggest strong environmental drivers rather than population-wide changes in genetics or willpower. As seen for cardiometabolic health, however, the complex effects of different foods and diet patterns may be more relevant for long-term weight homeostasis than reductionist approaches focused on total calories. For short-term weight loss, total calories are most relevant, which is why almost any type of diet may initially work. For long-term weight maintenance, however, and more 53 importantly for cardiometabolic health, healthful food-based patterns appear especially important. Humans have multiple, redundant biologic mechanisms to maintain weight homeostasis. Current 3 concepts postulate that different foods may, over years, help or hinder these intrinsic mechanisms. For 18,199 example, foods rich in refined grains, starches, and sugar appear especially harmful, driving 200-204 obesogenic pathways. Other foods, such as milk, appear relatively neutral, neither helping nor 199,205 perturbing homeostatic mechanisms for long-term weight control. Effects of meats, cheese, and eggs may vary as to whether they are eaten with refined carbohydrates (in which case they seem to worsen weight gain) or in place of refined carbohydrates (which are associated with less weight gain or even 199 relative weight loss). Also, fruits, nonstarchy vegetables, beans, nuts, yogurt, fish, and whole grains 9,18,199,205 appear to protect against chronic weight gain. Mechanisms underlying these observations are 203 200 being elucidated but may involve satiety, brain craving and reward, glucose-insulin responses, 201 206 202 204 hepatic fat synthesis, adipocyte function, visceral adiposity, metabolic expenditure, and the gut 18,199,205,207-209 microbiome. Because habitual excess energy intakes as small as 50 to 100 kcal/day may 67 explain much of the obesity epidemic, very subtle effects on these pathways may be sufficient, when sustained, to account for population shifts in weight. For example, lower sleep duration and altered circadian rhythms predict weight gain and obesity, altered hunger and food 18,210 preferences, and changes in leptin, ghrelin, insulin, and gut-peptide concentrations. Increasing physical activity has complementary benefits on weight maintenance and metabolic health. More liquid calories, larger portion sizes, and more meals away from home are also linked to risk of adiposity. Changes in social norms and networks, industry marketing, and local food availability also 216-218 appear important. In summary, these complex and often insidious influences can make unintended weight gain very easy. Conversely, these drivers can also serve as positive levers to attenuate or reverse chronic energy gaps, weight gain, and adiposity. Regardless of body weight, overall dietary quality strongly influences 3,53 cardiometabolic health, analogous to weight-independent health benefits of physical activity. In contrast, other conventional dietary metrics, such as calorie content, total fat, and energy density, may not 18,199,205 reliably identify how specific foods influence long-term weight gain. Dietary Patterns Dietary patterns represent overall combinations of foods consumed, which together can produce synergistic health effects. Evidence-based beneficial diet patterns share several key characteristics: more minimally processed, bioactive-rich foods, such as fruits, nuts/seeds, nonstarchy vegetables, beans, whole grains, seafood, yogurt, and vegetable oils, and fewer red meats, processed (sodium-preserved) meats, and processed and packaged foods rich in refined grains, starches, added sugars, salt, and trans fat (Table 49. Randomized trials in both primary and secondary prevention populations confirm cardiometabolic 17,132,219,220 benefits of such healthful, food-based diet patterns. In comparison, observational cohorts and randomized trials confirm little clinical effect of diets focused on isolated nutrient targets, such as low- 119-121,125 fat, low-saturated fat diets. Because sodium and trans fats can be added to or removed from otherwise similar foods and dietary patterns, a specific nutrient focus on these industrial additives is 53 warranted. Focusing on overall diet patterns can lead to health benefits from modest changes across multiple foods, rather than large changes in a few factors, potentially increasing effectiveness and compliance. This flexibility can also facilitate behavioral counseling, permitting a more personalized 53 focus (Table 49. Estimating the global and regional burden of suboptimal nutrition on chronic disease: methods and inputs to the analysis. For most dietary factors, evidence is derived from controlled trials of risk factors plus long-term prospective cohorts of disease endpoints. Other popular dietary patterns include vegetarian or vegan, low-carbohydrate, and “paleo” diets. People who follow these patterns may be health conscious and tend to make better choices. Yet, these dietary patterns can vary dramatically in their healthfulness; each can range from excellent to poor, depending on the specific foods selected. A cardioprotective diet pattern is best characterized by being rich in specific healthful foods (see Table 49. Changing Behavior Because dietary changes can be low risk, low cost, and broadly available, strategies for effective 216,217,221 behavior change are essential at individual, health system, and population levels. Clinical (Individual-Based) Strategies Numerous controlled trials have identified effective approaches for individual behavior change: setting proximal, targeted goals; self-monitoring; regular feedback; peer support; increasing self-efficacy; and 221,222 motivational interviewing. These strategies should be incorporated into practice to improve specific dietary priorities. Providers should remember that patient compliance with both lifestyle counseling and medication prescriptions is similarly incomplete, yet such strategies, even imperfectly implemented, 223 improve clinical outcomes. Novel Technologies Novel personal technologies such as mobile applications (mHealth), Internet programs, and personal devices (e. Optimally, deployment of these approaches should incorporate established individual-based behavior change strategies. A systematic review of randomized trials and quasi-experimental studies demonstrated general effectiveness of these approaches for dietary 224 change and/or weight loss. While promising, most of these studies had a duration of 6 weeks to 6 months and thus require evaluation of long-term effectiveness and sustainability. Health Systems For many clinicians, certain barriers may limit their ability to implement effective behavior change strategies: limited patient visit time, insufficient financial or other provider incentives, suboptimal knowledge or experience, and inadequate electronic tools for assessing diets and monitoring changes over time. Specific health system changes, now being introduced for tobacco and obesity control, can support 217,222,225,226 and facilitate behavior change. Integrated systems can provide coordinated care by multidisciplinary teams; with alignment of payments, practice goals, and quality benchmarks to reward dietary change efforts. Policy Strategies Given the key roles of social and environmental forces in shaping dietary habits, policy (population- based) approaches are crucial to achieve broad success.
Although secondary analyses of several primary prevention trials have also shown a risk reduction in older subsets purchase super levitra us impotent rage random encounter, the benefits of statins for primary prevention in this age-group are less clear than for secondary prevention generic super levitra 80mg with amex erectile dysfunction naturopathic treatment. For older adults already receiving high- dose statins and tolerating them well, the guidelines do not recommend lowering the dose. The most common side effect observed with statins is 178 myalgia, which occurs in about 5% of patients. Myopathy documented by elevated muscle enzyme levels is much less common, occurring in 0. The combination of gemfibrozil and statins is associated with an increased risk of rhabdomyolysis (0. Diabetes Advancing age is accompanied by reduced insulin sensitivity and secretion, contributing to greater glucose intolerance and higher rates of type 2 diabetes mellitus in older adults (see also Chapter 51). Approximately 15% of adults 65 years of age or older have diagnosed diabetes, and in another 7% 29 diabetes is undiagnosed. In older adults, diabetes is often underdiagnosed due to the absence of classic symptoms. The primary treatment goals for older adults with diabetes include managing hyperglycemia and reducing the risk of adverse clinical outcomes. Dietary interventions that optimize macronutrient content as well as calorie count help improve glycemic control, independent of weight change. Despite the benefits of lifestyle interventions, most older diabetic patients require medications to achieve glycemic control. Because several large clinical trials have found either no effect or even increased mortality rates in older patients receiving intensive glycemic therapy, a less-intensive target HbA1c of 7% to 7. Even higher targets may be considered for older 182 patients with frailty or a short life expectancy. Metformin is favored as a first-line therapy due to its low risk for hypoglycemia and other adverse effects. Additional options include the short-acting sulfonylurea glipizide and the short-acting insulin 29 secretagogue repaglinide. If insulin therapy is needed, ultra–long-acting basal and very short-acting prandial insulins are strongly preferred over intermediate-acting insulin formulations. Risk reduction from smoking cessation was seen even in persons age 80 years or 184 over. Smoking cessation also reduces the risk of new or recurrent stroke and improves claudication symptoms. Because the biologic and clinical repercussions of a sedentary lifestyle exacerbate age-related pathophysiologic changes, the health consequences and societal costs of physical inactivity are especially relevant to older adults. Physical inactivity results in decreased functional capacity, increased risk of falling, worsened psychological status, and reduced cognitive function. Only 18% of persons 75 years or older reported regular moderate or vigorous physical activity, and only 14% of men and 8% of women 65 years or older reported aerobic and muscle-strengthening activities that met the 2008 federal physical activity guidelines. In the Honolulu Heart Program, relatively healthy men 71 to 93 years old who walked more than 1. Physical Activity Prescription The most important consideration when counseling regarding physical activity is to help shape a program that is pleasurable and achievable, and that avoids injury or exacerbation of comorbid problems. Aerobic activity, strength activity, balance, and flexibility are all vital components. For adults willing to enter a formal exercise program, specific exercises can help improve tolerance of the physical demands of daily living and recreational activities. Generally, work intensities start lower than in younger patients, with smaller increments over time, especially in those with significant comorbidities that limit mobility (e. Increasing the frequency and duration of exercise sessions should supersede increases in intensity to reduce the potential for overuse injuries. For adults who are disinclined to exercise in a program, increasing activity as part of daily living is also beneficial. Regular leisure activities such as housekeeping, walking, and gardening are all healthful. Accumulating evidence suggests that activity benefits may increase in proportion to intensity. Reports in patients with established heart disease, including one study of patients with a mean age of 75 years, suggest that high-intensity aerobic interval training can elicit greater improvement in exercise capacity 29 than continuous exercise at a lower intensity. Despite these encouraging data, such training is more complex than traditional training, necessitating more supervision for implementation and safety. Larger studies are needed to establish the efficacy and safety of high-intensity interval training in older patients. Cardiac Rehabilitation Cardiac rehabilitation consists of structured exercise training combined with secondary prevention reinforcement, including an individualized exercise prescription as well as close supervision and support 29 (see also Chapter 54). It can be particularly helpful in catalyzing physical activity and wellness in adults who are sedentary amidst illness, deconditioning, and entrenched behavior patterns. Unfortunately, the vast majority of older patients do not participate in cardiac rehabilitation due to multiple factors, including lack of referral, logistical barriers, or socioeconomic barriers. Failure to refer, particular for women, is a major contributor to the low participation of older adults. Participation in 29 cardiac rehabilitation by Medicare-eligible recipients is only approximately 12%. Between 1988 and 1994 and 2007 and 2008, obesity rates increased 30% to 40% in older women and 67% to 100% in older men. Given the higher mortality rates in old age, the mortality risk attributable to obesity is higher in older adults. Diet Undernutrition is more common in older than younger individuals due to a combination of medical and socioeconomic factors: 5% to 10% of community-dwelling persons age 70 years or older are undernourished, and the prevalence increases to 30% to 65% in institutionalized elders. It is useful for cardiologists and primary care providers to assess the dietary intake of older patients, provide general dietary advice, and refer to a nutritionist if a major dietary deficiency or malnutrition is suspected. Vitamin and mineral deficiencies are common in seniors due to inadequate intake, decreased absorption, and the effects of disease and medications. Some of these benefits may emanate from flavonoids, which are abundant in fruits, vegetables, nuts, tea, and wine, and have antiinflammatory and antioxidant effects. Noncardiac Surgery and Perioperative Management Considerations in Older Adults The number of individuals over 70 years of age undergoing surgical interventions has increased dramatically and continues to expand. Perioperative management in older adults poses distinctive age- related challenges. Advance directives are important and patients should identify a health care proxy. Suspending a do-not-resuscitate designation is common during procedures, but it is important to clarify management plans should an adverse outcome ensue. Gait speed, a marker of frailty, has been recognized as an important predictor of adverse outcomes even beyond standard assessments by the Society of Thoracic Surgery scoring system; a slow gait speed (≥0. Age-related changes alter drug pharmacodynamics and pharmacokinetics, rendering older patients more vulnerable to anesthetic and analgesic complications. Although regional (epidural) anesthesia does not generally decrease the mortality risk or risk of postoperative delirium or cognitive dysfunction, it is associated with better peripheral vascular circulation, less blood loss, improved pain control, reduced ileus, attenuation of thromboembolic complications, fewer respiratory complications, reduced postoperative narcotic requirements, and a reduced surgery stress response. Delirium is a frequent complication in older adults, with an incidence of 40% to 191 52%.