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A side-biting clamp is now placed on the ascending aorta so that the marked area is centered in the clamp calcitriol 0.25 mcg with mastercard. The pericardium is loosely approximated with a Gore-Tex pericardial membrane calcitriol 0.25mcg discount, a small chest tube is placed in the anterior mediastinum cheap calcitriol 0.25 mcg on-line, and standard sternotomy closure is performed discount calcitriol 0.25 mcg amex. Aortic Partial Occlusion the side-biting clamp must be placed carefully on the ascending aorta, especially in neonates and infants with small aortas to avoid hypotension or myocardial ischemia secondary to compromised coronary flow. Before incising the aorta, the position of the clamp should be tested to ensure that no hemodynamic changes are going to occur. Multiple reapplications of the clamp from different angles may be required before a satisfactory placement is found. Coronary Ischemia It can be challenging to apply the partial occluding clamp while on cardiopulmonary bypass without causing coronary insufficiency. Marking the future site of the central shunt on the ascending aorta is helpful so as to maintain orientation when the aorta is open and decompressed. Thrombosis or Distortion of the Graft above the Aortic Anastomosis the length of graft beyond the side-to-side anastomosis is crucial with this technique. If too much graft extends above the aortic anastomosis, there will be an area of relatively stagnant flow that may predispose to graft thrombosis. If too little graft remains, the suture line may distort or compromise flow into the graft from the aorta. If the graft has been cut too short, the end can be closed with a circular piece of Gore-Tex graft cut from extra graft material. Coronary Ischemia It can be challenging to apply the partial occluding clamp while on cardiopulmonary bypass without causing coronary insufficiency. Marking the future site of the central shunt on the ascending aorta is helpful so as to maintain orientation when the aorta is open and decompressed. Melbourne Shunt For patients with severe pulmonary atresia and confluent pulmonary arteries, it can be efficacious to transect the main (diminutive) pulmonary artery and anastomose this directly to the posterior aspect of the ascending aorta, thereby creating the equivalent of a central shunt without the use of prosthetic graft. Some suggest that this configuration maximizes pulmonary artery growth in part because of the growth potential (and lack of restriction) of the main pulmonary artery when compared with Gore-Tex ( 18. Right-Sided Modified Blalock-Taussig Shunts the aorta and superior vena cava are retracted away from each other, and the posterior pericardium is incised above the superior margin of the right pulmonary artery. Dissection around the Right Pulmonary Artery There are many adhesions and collateral vessels in this area. Right Pulmonary Artery Stenosis If significant stenosis is present at the insertion site of the shunt into the right pulmonary artery, the tube graft should be divided after the initiation of cardiopulmonary bypass. The transected end should be secured with at least two adequately sized metal clips or oversewn with a 6-0 or 5-0 Prolene suture. The residual Gore-Tex material should then be removed from the right pulmonary artery and this area is enlarged with an oval-shaped patch of autologous pericardium or pulmonary homograft. Division of the Gore-Tex Shunt Theoretically, as a child grows, an intact Gore-Tex tube graft may cause upward traction on the right pulmonary artery, which may lead to distortion and possible late development of pulmonary artery stenosis. If an adequate length of Gore-Tex tube graft can be dissected free without incurring excessive bleeding, the tube may be secured with two metal clips on each side and divided to prevent this potential late complication. Left-Sided Modified Blalock-Taussig Shunts Isolation of the left-sided shunt is somewhat more cumbersome and can be accomplished in many ways. Alternatively, the left pulmonary artery is dissected free from within the pericardium, and the Gore-Tex tube graft is clipped just above its junction with the pulmonary artery. Central Shunt With the initiation of cardiopulmonary bypass, the Gore-Tex tube graft is occluded with a metal clip. Prosthetic Ascending Aorta-Right Pulmonary Artery Shunt the tube graft is carefully dissected free from the lateral aspect of the ascending aorta and occluded with a metal clip as cardiopulmonary bypass is commenced. Usually, the shunt tubing is divided while on bypass and the aortic and pulmonary ends are oversewn with a running 6-0 or 5-0 Prolene suture. The correct plane for dissection must be identified, staying right on the Gore-Tex graft itself to avoid entry into the aorta. If the shunt cannot be safely dissected from the aorta, it should be occluded as much as possible with a vascular clamp or forceps when cardiopulmonary bypass is commenced and the dissection completed with the patient on bypass. Waterston and Potts Shunts Waterston and Potts shunts are no longer performed, but familiarity with the techniques of their closure is essential for the surgeon who operates on patients who have undergone these shunting procedures in the past. Technique: Waterston Shunt the easiest way to close a Waterston shunt is on cardiopulmonary bypass with the aorta cross-clamped. After administering cardioplegic solution, a small transverse aortotomy is made, and the shunt may be closed from within the aorta with a few interrupted sutures. The preferred method is to detach the right pulmonary artery from the aorta and oversew the defect in the ascending aorta with a running 5-0 Prolene suture. The defect in the pulmonary artery can be closed transversely by direct suture or preferably patched with a piece of autologous pericardium or pulmonary homograft. Pulmonary Artery Distortion If the shunt has created some stenosis or kinking of the right pulmonary artery, this should be reconstructed with an appropriate pericardial or homograft patch. Flooding of the Pulmonary Circulation the site of the shunt must be occluded with the initiation of cardiopulmonary bypass, or flooding of the lungs will occur. If this cannot be achieved with a vascular forceps or clamp, the right and left pulmonary arteries should be encircled before beginning cardiopulmonary bypass, and snared or clamped. Technique: Potts Shunt Closure of Potts shunt is performed on cardiopulmonary bypass with moderate hypothermia. The patient is placed in the Trendelenburg position, and with the heart decompressed, the perfusion pressure is temporarily reduced. The site of a shunt orifice in the left pulmonary artery is identified and closed with a purse-string suture or patch. Flooding of the Pulmonary Circulation Before instituting cardiopulmonary bypass, the site should be identified by palpating for a thrill along the left pulmonary artery. Air Embolism through Aortic Opening When the left pulmonary artery is opened, some flow must be maintained through the aortic cannula to prevent air embolism. In addition, there is a real or potential slit-like opening, the foramen ovale, where the fossa ovalis flap disappears behind the superior septal limbus. Generally, the higher pressure in the left atrium keeps the fossa ovalis flap in apposition to the superior septal limbus, and therefore the opening remains closed. In 20% of the population, however, the foramen ovale is patent and has the potential to allow shunting under certain circumstances. When pressure in the right atrium increases, as in right- sided heart failure, the septum becomes stretched and allows the foramen ovale to enlarge with significant shunting at the atrial level. The sinus venosus atrial septal defect occurs high in the atrial septum and extends into the orifice of the superior vena cava, which becomes malpositioned slightly toward the left. There is usually anomalous drainage from the right superior pulmonary vein associated with these defects. This defect occurs in the midseptum in the vicinity of the fossa ovalis and may be small or very large. Infrequently, the defect may occur low in the septum and extend into the orifice of the inferior vena cava, which also becomes malpositioned toward the left. This type of defect is sometimes referred to as a sinus venosus defect of the inferior vena caval type and may be associated with anomalous pulmonary venous drainage. A defect low in the interatrial septum that extends down to the level of the atrioventricular valve orifices is part of the atrioventricular septal defect complex (see Chapter 22). Systemic venous return flows in from opposing directions through the superior and inferior venae cavae into the sinus venarum. This smooth-walled area is the most posterior portion of the right atrium and stretches between the orifices of the caval veins. From the viewpoint of the surgeon looking down into the right atrium, the sinus venarum is more or less horizontal with the superior vena cava entering from the left and the inferior vena cava (bounded by the eustachian valve) entering from the right. Just below and medial to the orifice of the superior vena cava arises a muscle bundle, the crista terminalis, which springs into prominence as it circles the orifice of the superior vena cava to the right lateral wall of the atrium and continues inferiorly toward the inferior vena cava, thereby forming the boundary between the sinus venarum and the atrial appendage. Lying subepicardially in the sulcus terminalis, just below the entrance of the superior vena cava, is the sinoatrial node, which may be vulnerable to injury from the various surgical incisions and cannulations commonly performed on the right atrium. In contrast with the smooth-walled sinus venarum, the lateral wall of the atrial appendage is ridged with multiple narrow bands of muscle, the musculi pectinati. Functionally, they supply the right atrium with enough pumping capacity to propel the venous inflow through the tricuspid valve into the right ventricle. Just above the sinus venarum in the center of the medial wall is the fossa ovalis, a horseshoe- or elliptically shaped depression. The true interatrial septum consists of the fossa ovalis with variable contributions from the superior, anterior, and inferior limbic muscle bundles that surround it. The aortic root is hidden behind the anteromedial atrial wall between the fossa ovalis and the termination of the heavily trabeculated right atrial appendage.

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Cardiac injury with hemorrhagic myocardial necrosis is a rare but known adverse effect of high-dose cyclophosphamide cheap 0.25mcg calcitriol free shipping, one of the most commonly used chemotherapy agents in conditioning regimens buy calcitriol toronto. Risk factors for cyclophosphamide cardiotoxicity include the use of doses equal to or greater than 120 mg per kg cheap 0.25mcg calcitriol visa, an underlying diagnosis of lymphoma order 0.25mcg calcitriol, prior radiation to the mediastinum or left chest wall, older age, and prior abnormally low cardiac ejection fraction [62,63]. Patients who had prior 2 cumulative anthracycline exposures of 550 mg per m doxorubicin equivalents are at an increased risk for developing heart failure. Signs and symptoms of congestive heart failure may occur within a few days of receiving cyclophosphamide, whereas anthracycline-related cardiomyopathy may have a delayed onset. Management involves careful assessment of volume status and discontinuation or adjustment of the drug levels of the offending agent(s). Several other agents, including eculizumab and defibrotide, have been effective in limited numbers of patients [71]. Most patients respond to conventional antihypertensive therapy, such as a calcium-channel blocker, angiotensin-converting enzyme inhibitor, or β- blocker. Measures to prevent hemorrhagic cystitis include aggressive fluid hydration to increase urine volume that dilutes and minimizes contact of acrolein with the mucosa, and administration of the drug mesna, which provides free thiol groups to detoxify acrolein. Unless there is evidence of disseminated infection, viral cystitis is managed with supportive therapy, including hydration and platelet transfusions. Central Nervous System Noninfectious complications include cerebrovascular events and encephalopathies due to metabolic, toxic, and immune-mediated causes. Focal symptoms are more indicative of infectious or cerebrovascular mechanisms, whereas diffuse symptoms such as delirium or coma may have metabolic causes. Thrombocytopenia poses a risk for intracranial hemorrhage, which usually presents as abrupt onset of focal neurologic deficit or mental status changes [77]. Several agents used in conditioning regimens may cause encephalopathy, including high-dose busulfan and high-dose cytarabine. Seizure prophylaxis with Keppra, Ativan, or phenytoin should be considered during conditioning with high-dose busulfan or carmustine, particularly for young children. Contributing factors may include hypercatabolism induced by conditioning, glucocorticoids, or sepsis, and high nitrogen loads associated with parenteral nutrition or intestinal hemorrhage. Treatment involves hemodialysis and administration of ammonia- trapping agents, such as sodium benzoate or sodium phenylacetate. Glucocorticoid therapy may be associated with psychosis, mania, or delirium in a dose-dependent fashion. Seizures or altered sensorium may be associated with the use of sedative-hypnotic drugs and have been reported as adverse side effects of many of the commonly used antibiotics and antiviral agents. Treatment of metabolic encephalopathies should be directed at the underlying problem and discontinuation of any offending drugs. A unique and usually reversible syndrome of cortical blindness has been reported as a complication of cyclosporine treatment; hypertension and hypomagnesemia are thought to be predisposing factors [83]. Hemolysis mediated by major or minor blood group incompatibilities is only seen in recipients of allografts. In the rare cases of ongoing hemolysis due to persistence of donor-directed isohemagglutinins, additional therapy with immunosuppressive agents, erythropoietin, plasma exchange, anti-B-cell antibodies (rituximab), or plasma exchange may be considered [88]. Hospitalized patients should be housed in single rooms that have positive-pressure air flow and ventilation systems with rapid air exchange and high-efficiency particulate air filtration [90]. Strict visitation, hand washing, and isolation policies should be instituted to prevent introduction or spread of communicable disease. A daily program of skin and oral care should include bathing all skin surfaces with mild soap, brushing teeth with a soft brush, frequent rinsing of the oral cavity with saline, and good perineal hygiene. The diet should exclude foods known to contain bacteria or fungi, and patients should avoid exposure to dried or fresh plants or flowers. Before Engraftment Period the period before engraftment (less than 30 days posttransplant) is characterized by neutropenia and oral and gastrointestinal mucosal damage. The use of indwelling central venous catheters heightens the risk of blood infections with organisms that colonize the skin, such as coagulase-negative staphylococci or Candida spp. Clostridium difficile toxic colitis can be a common infection in transplant patients, particularly those patients in intensive care units. Prophylactic systemic antibiotics are conventionally administered to reduce the risk of bacteremia during the neutropenic period, although improvement in survival has not been demonstrated [90]. Other causes of fever of unknown origin after engraftment include occult sinusitis, hepatosplenic candidiasis, and pulmonary or disseminated Aspergillus infection. Evaluation and Treatment Signs and symptoms of infection may be diminished in patients who are neutropenic or receiving immunosuppressive drugs. Thus, preemptive antibiotic therapy should be instituted promptly for any fever during the neutropenic period because infections can progress rapidly to a fatal outcome [90]. The febrile patient should be examined thoroughly for source of infection, including the oral cavity, perianal tissue, and skin surrounding the central venous catheter. Cultures should be obtained of blood, urine, and stool if diarrhea is present; and chest radiograph should be performed. Broad-spectrum antibiotic therapy should be continued through the duration of neutropenia, even if fever resolves. If fever persists, the antibiotic regimen should be broadened after 4 days to provide empiric treatment of fungi. Evaluation of persistent fevers after granulocyte recovery should consider occult sources of bacterial infection, such as sinuses, perirectal tissue, or central venous lines, as well as viral or fungal etiologies. The diagnosis is established by biopsy or brushings taken from the center of the lesions so as to include infected endothelial cells and submucosal tissue. Infectious causes of pulmonary infiltrates must be differentiated from noninfectious causes to ensure prompt institution of appropriate therapy [55]. Transbronchial biopsy is not recommended because it has not been shown to improve sensitivity in these situations, and often thrombocytopenia precludes the ability to perform the procedure safely. Fine-needle aspiration has a sensitivity of approximately 67% for diagnosis of fungal infection, but it has a poor negative predictive value. Specimens should be evaluated histologically and undergo testing for bacteria, fungi, and viruses by appropriate cultures and immunocytochemical stains as noted previously. The diagnosis of invasive candidiasis is difficult because blood cultures are negative in approximately one-half of the cases with organ involvement. Lipid-complexed amphotericin products, echinocandins, or other azoles may be useful alternatives [106]. Because fungal vegetations on heart valves may occur, echocardiography should be considered to evaluate for this. Aspergillus infections have been difficult to diagnose by standard methods, and more than 20% of the cases have been diagnosed only at autopsy. The Aspergillus Galactomannan Enzyme Immunoassay detects a polysaccharide secreted from Aspergillus hyphae and is a useful screening tool, with a sensitivity of 65% and specificity of 95% [109]. Because invasive aspergillosis is associated with a high mortality rate, documented or suspected infections should be treated aggressively with voriconazole or another mold-active azole, lipid-complexed amphotericin products, or combination therapy [110]. Foscarnet can be used in place of ganciclovir if significant marrow toxicity occurs or drug resistance is identified. For localized infection, a short course of intravenous acyclovir for 24 to 48 hours can be followed by oral valacyclovir for the duration of therapy. Symptoms of upper respiratory infection should prompt cultures of nasopharyngeal secretions, careful monitoring for progression of disease, and isolation to prevent spread to other patients. When disseminated, adenovirus can cause hemorrhagic enterocolitis, interstitial pneumonitis, myocarditis, nephritis, meningoencephalitis, or severe hepatitis. Patients with poor T-cell function, such as recipients of T-cell–depleted grafts or those receiving intensive immune-suppressing therapies, are at greatest risk for disseminated infection. The most promising treatment results have been reported after administration of cidofovir, although renal insufficiency is a potential side effect [133]. Graft Rejection Graft rejection presents as failure to recover hematopoiesis after transplantation, termed primary graft failure, or as the loss of an established donor graft, termed secondary graft failure. Persistence of neutropenia (an absolute neutrophil count of more than 100 cells per µL) after day 26 is associated with increased risk of early mortality [139]. Although the molecular and cellular mechanisms are not completely understood, graft rejection appears to be mediated preferentially by recipient T cells [140]. In either case, graft failure after myeloablative conditioning is a life-threatening complication because autologous reconstitution is uncommon and results in death from hemorrhage or infection. A range of cellular therapies have been used to overcome rejection ranging from donor lymphocyte infusions in the case of declining donor T-cell chimerism, possibly combined with immunosuppressive therapy. Preferentially, conditioning should differ from that used at the first transplant to avoid unnecessary toxicity, and a high graft cell dose is recommended. The clinicopathologic syndrome is consistent with various combinations of inflammatory dermatitis, enteritis, and hepatitis, which reflect the pathophysiology of T-cell activation with generation of cytotoxic lymphocytes and elaboration of inflammatory cytokines that cause tissue damage.

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Traditionally cheap calcitriol 0.25mcg amex, this complication has been dealt with by fixing the ascending aorta to the back of the sternum buy calcitriol 0.25mcg line. Results with this procedure are inconsistent cheap calcitriol 0.25mcg fast delivery, and aortopexy may be contraindicated if further cardiac procedures are anticipated cheap calcitriol 0.25mcg with amex, as in single ventricle patients. In these cases, the obstructing septum can sometimes be resected, or more often is used to secure the ventricular septal defect patch in a manner that “pulls” the septum out of the subvalvar region. Other patients with prohibitively small left ventricular outflow tracts may require a Yasui-type reconstruction. This operation has also been used for the uncommon patient with hypoplastic left heart syndrome, two adequate-sized ventricles, and a ventricular septal defect. The aortic arch repair is completed with the Damus-Kaye-Stansel similar to that of a Norwood reconstruction so as to make a gentle taper between the smaller descending aorta and the large Damus- Kaye-Stansel neo-aortic root. The right ventriculotomy in this operation, like that in a Ross procedure, must acknowledge that the pulmonary valve extends quite inferiorly and may need to be lower on the right ventricular free wall. The superior tip of the baffle will be secured to the most superior/anterior portion of the ventriculotomy, and the inferior tip of the baffle near the muscle of Lancisi. The right ventriculotomy is then used for the proximal site of the right ventricle to pulmonary artery connection. Using the right ventriculotomy, a homograft connection is created between the right ventricle and transected main pulmonary artery, thus creating a two-ventricle repair. The anatomic features include aortic valve atresia or severe stenosis, with marked hypoplasia or absence of the left ventricle. The ascending aorta is small, usually only 2 to 3 mm in diameter, and the mitral valve is hypoplastic or atretic. Other single-ventricle complexes may present with evident or potential left ventricular outflow tract obstruction. These include tricuspid atresia with transposition of the great arteries and single ventricles with left ventricular outflow chambers. Pulmonary artery banding in this subgroup of patients may predispose to the development of subaortic obstruction. The Norwood principle can be applied to all patients with single-ventricle morphology and real or potential obstruction to systemic flow. It involves the creation or preservation of optimal hemodynamics and anatomy in preparation for a successful Fontan procedure. The aorta must be associated directly with the single ventricle in such a way as to provide unobstructed flow from the single ventricle to the systemic circulation and to allow potential for growth. Pulmonary blood flow must be regulated to avoid the development of pulmonary vascular disease, and minimize the volume load on the single ventricle to preserve long-term ventricular function. When there is stenosis or atresia of the left-sided atrioventricular valve, a large interatrial communication must be created to avoid the development of pulmonary venous obstruction and hypertension. Preoperative management includes continuous infusion of prostaglandin E to maintain patency of the ductus arteriosus. A particularly restrictive interatrial communication limits pulmonary overcirculation, and a balloon atrial septostomy or blade septectomy may result in hemodynamic deterioration and should be avoided. In contrast, a truly restrictive atrial component may increase pulmonary vascular resistance and significantly increase perioperative mortality. In this scenario, a careful balloon septostomy may relieve this obstruction without incurring pulmonary overcirculation. In addition, hyperventilation and increased inspired oxygen concentrations may decrease pulmonary vascular resistance, leading to increased pulmonary blood flow at the expense of decreased systemic perfusion. Traditionally, this operation has been performed with the use of deep hypothermic arrest for the aortic reconstruction. More recently, techniques using selective cerebral perfusion to avoid or minimize circulatory arrest have been adopted in most institutions. If a Sano-type right ventricle-to-pulmonary artery conduit is to be used, the “top hat” can be created prior to sternotomy with a tube graft (usually 5 to 6 mm) and a piece of Gore-Tex patch with an appropriate-sized defect created with a skin punch. The arterial cannula is deaired and introduced several millimeters into the Gore-Tex chimney, and the purse-string suture is tightened. The tapes around the pulmonary arteries are placed on traction to prevent pulmonary blood flow and ensure satisfactory systemic perfusion. During the cooling period, the ascending aorta is dissected away from the main pulmonary artery and the branch vessels of the aortic arch are mobilized. The innominate, left carotid, and left subclavian arteries are looped with Silastic tapes on tourniquets. The distal aortic arch and descending aorta are mobilized down to the level of the left bronchus with blunt dissection. For patients with significant transverse aortic arch hypoplasia, a second ductal cannula may improve lower body perfusion and cooling. Patients with severe aortic atresia (ascending aorta <2 mm) require careful handling of the aorta during dissection so as not to distort the great vessel and cause coronary ischemia. Procedure After cooling for at least 15-20 minutes to a temperature of 18°C, the second limb of the arterial circuit is flushed and secured to the Gore-Tex tube. Alternatively, a single arterial line is used, and during a brief period of hypothermic arrest, the arterial cannula is removed from the pulmonary artery and placed into the tube graft. The previously placed tourniquets are used to occlude the proximal innominate artery, the left carotid, and left subclavian artery. The ductus arteriosus is transected, and the pulmonary end is ligated or oversewn with a running 6- 0 Prolene suture. The main pulmonary artery is transected at the level of the takeoff of the right pulmonary artery. The defect in the distal pulmonary artery is then closed with either a patch of Gore-Tex if an aortopulmonary shunt is to be used, or with the Sano “top hat” created previously. Myocardial Preservation With the descending thoracic aorta and arch vessels occluded, cold blood cardioplegic solution is infused into the side port of the arterial cannula. This perfuses the coronary circulation by retrograde flow through the ductus, arch, and ascending aorta. Tourniquets are tightened around innominate, left carotid, and left subclavian arteries during low-flow cerebral perfusion. A brief period of circulatory arrest or continued low-flow cerebral perfusion providing venous return with a pump sucker is used to excise the septum primum. This can be accomplished through the right atrial cannulation site by temporarily removing the venous cannula. Alternatively, a small right atriotomy is made and closed with a 6-0 Prolene suture after creating an adequate interatrial communication. The opening is carried proximally along the lesser curvature of the aortic arch and down the left side of the ascending aorta. Retained Ductal Tissue All the ductal tissue in the aortic arch and descending aorta must be excised, including resection of the coarctation ridge, if present. Sewing to ductal tissue may result in bleeding from the suture line or even dehiscence of a portion of the anastomosis. The descending aortic segment is then anastomosed to the posterolateral aspect of the distal arch opening with a running Prolene suture. An oval patch of pulmonary homograft is tailored to reconstruct the proximal descending aorta, aortic arch, and ascending aorta. The anastomosis of the pulmonary homograft to the aorta is started at the most distal extent of the incision on the descending aorta with a 7-0 Prolene double-armed suture. The posterior suture line is continued onto the ascending aorta, stopping 5 mm above the proximal extent of the incision. The anterior suture line is accomplished with the other needle, again ending the suture line 5 mm short of the proximal ascending aortic opening. Patch Material A patch cut from an adult-sized pulmonary homograft has a natural curved shape, which mimics the curve of the underside of the aortic arch. However, there are availability and cost issues, as well as concerns regarding viral transmission and the generation of cytotoxic antibodies, which may limit transplant options. Some surgeons have advocated the use of bovine pericardium or other substitutes, using two pieces cut in a curved shape and sewn together along their concave aspect to create an appropriately shaped aortic arch patch. Suturing along Arch Alternating traction on the left carotid tourniquet and the innominate artery tourniquet improves the exposure for performing the posterior and anterior suture line on the underside of the aortic arch.

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In patients who demonstrate more severe purchase cheap calcitriol on-line, life-threatening septic shock discount calcitriol online master card, an aminoglycoside should be combined with a fourth-generation cephalosporin cheap calcitriol 0.25mcg, an antipseudomonal penicillin (ticarcillin-clavulanate or piperacillin-tazobactam) or a carbapenem (see Chapter 2) buy calcitriol canada. Prevention Patients with frequent symptomatic recurrences should receive preventive therapy. Antibiotic prophylaxis for patients with indwelling bladder catheters is not effective and simply selects for antibiotic-resistant pathogens. Causes and Pathogenesis Gram-negative bacteria are the most common cause of prostatitis. The mechanism by which bacteria usually reach the prostate is reflux of infected urine. The prostate contains a potent antibacterial substance called prostatic antibacterial factor. The production of this zinc-containing compound is markedly reduced during prostatitis, allowing active growth of bacteria. Symptoms and Clinical Findings Patients with acute bacterial prostatitis experience fever, chills, dysuria, and urinary frequency. If the prostate becomes extremely swollen, bladder outlet obstruction may develop. Vigorous palpation of the prostate may precipitate bacteremia and therefore, prostate examination should be gently performed. Symptoms can mimic cystitis; however, it is important to keep in mind that males rarely develop isolated cystitis, and prostatitis is far more likely. Back pain, low-grade fever, myalgias, and arthralgias are the most common complaints. Diagnosis In acute bacterial prostatitis, massage of the inflamed prostate is contraindicated because of a high risk of precipitating bacteremia. Diagnosis and treatment of chronic prostatitis is difficult, and is best managed by an experienced urologist. Quantitative culturing of the first void urine, midstream urine, and prostatic massage sample or post-prostatic massage urine sample are recommended to differentiate cystitis and urethritis from chronic prostatitis. Primarily caused by gram-negative enteric organisms: a) Escherichia coli is most frequent. Clinical manifestations: a) Acute prostatitis—fever, chills, dysuria, and urinary frequency; bladder outlet obstruction. It should be kept in mind that most antibiotics do not penetrate the lipophilic, acidic environment of the prostate; however, just as is observed in meningitis, the marked inflammation in acute prostatitis permits antibiotic penetration. Patients usually respond quickly to intravenous therapy, allowing the switch to an oral regimen. In chronic prostatitis, antibiotic penetration is critical for effective treatment. The fluoroquinolones have also proved effective for treatment of chronic prostatitis. The incidence of these infections rises in association with reductions in public health funding. The importance of aggressive case- finding and early treatment cannot be overemphasized. These infections are associated with a purulent or mucousy penile discharge in men and pyuria in women. Ureaplasma urealyticum and noninfectious causes (trauma, allergic, and chemical) also result in symptoms of urethritis, but are not associated with pyuria. Symptoms Patients with urethritis usually experience burning on urination but have no other symptoms. This symptom is usually accompanied by a urethral discharge that often stains the undergarments. The urethral discharge may vary greatly in quantity and color and can be primarily purulent or can also contain significant mucous. If a discharge cannot be expressed, a small calcium alginate urethral swab can be gently inserted at least 2 cm into the urethra. Urinalysis of the first 10 mL of urine, followed by a midstream sample, is useful for differentiating cystitis from urethritis. At the present time, diagnosis of this pathogen is usually presumptive and is based on clinical findings. Fluoroquinolones are no longer recommended because of the percentage of resistant strains. If urethritis is refractory to doxycycline, then azithromycin may prove effective. Causes: a) Chlamydia trachomatis and Neisseria gonorrhoeae are associated with a purulent discharge. Symptoms and signs: a) Burning on urination, worse with concentrated urine after alcohol consumption b) Staining of underwear, mucous in the urine. It is the most common gynecologic disease managed in emergency rooms, with an estimated 1 million cases being diagnosed annually in the United States. The disease is caused by spread of cervical microbes to the endometrium, fallopian tubes, ovaries, and surrounding pelvic structures. The vagina contains multiple organisms, with Lactobacillus being the predominant organism. The endocervical canal serves as a protective barrier, preventing the vaginal flora from entering the upper genital tract and maintaining a sterile environment. These two pathogens may be accompanied by growth of other pathogenic organisms, most commonly Streptococcus pyogenes and Haemophilus influenzae. Other, less common, pathogens include a) Streptococcus pyogenes and Haemophilus influenzae (most frequently accompany gonorrhea and chlamydia). The finding of right upper quadrant tenderness suggests the development of perihepatitis (Fitz–Hugh–Curtis syndrome), noted in about 10% of cases. The finding of increased tenderness in one adnexa or palpation of an adnexal mass suggests a tubo-ovarian abscess. Others diseases that may present with similar clinical findings—appendicitis, ectopic pregnancy, diverticulitis, adnexal torsion, rupture or hemorrhage of an ovarian cyst, nephrolithiasis, pancreatitis, and perforated bowel—should also be considered. Lower abdominal pain during or immediately following menses, a) made worse by jarring motions, b) accompanied by vaginal bleeding (one-third of cases), and c) commonly presenting with vaginal discharge. Diagnosis During the initial evaluation, a pregnancy test should be performed to exclude the possibility of tubo-ovarian pregnancy. Nevertheless, a number of other disorders can also cause a purulent discharge, giving the test a low specificity (approximately 40%). Laparoscopy should be reserved for patients who are seriously ill, and in whom another competing diagnosis such as appendicitis is suspected. It should also be performed in patients who remain acutely ill despite outpatient treatment or 72 hours of inpatient therapy. An imaging technique revealing thickened fluid-filled oviducts with or without free pelvic fluid or tubo-ovarian swelling. This regimen should be continued until 24 hours after significant clinical improvement, and should then be followed by oral doxycycline to complete 14 days of therapy. An alternative inpatient regimen consists of clindamycin and gentamicin, followed by oral clindamycin or doxycycline to complete 14 days of therapy (see Table 9. If tubo-ovarian abscess is suspected, or the patient fails to respond within 72 hours, laparoscopy should be performed and areas of loculated pus drained percutaneously or transvaginally. If a leaking or ruptured abscess is suspected, laparotomy should be performed immediately. Definitive diagnosis can be made by a) Laparoscopy (low sensitivity; should be reserved for the seriously ill patient). To prevent infertility and chronic pain, the threshold for treatment should be low. In India, Papua New Guinea, the West Indies, and parts of Africa and South America, donovanosis or granuloma inguinale (Klebsiella granulomatis) is a major cause of genital ulcers. Clinical Findings Certain clinical features tend to favor one causative agent over another. However, these rules should be applied with caution, because the “classic” findings are seen in only one-third of cases. Thus, the following physical findings, although specific, are insensitive (see Table 9. The number of ulcers has been purported to be helpful; however, because of the wide variability in ulcer number in each disease, recent studies indicate that this characteristic is not helpful. The location of the ulcers is helpful in differentiating Behçet’s syndrome from other causes.

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