Peter A. McCullough, MD, MPH, FACC, FACP

• Chief Academic and Scientifi c Offi cer
• Medical Director, Preventive Cardiology
• St. John Providence Health System
• Providence Park Heart Institute
• Novi, Michigan

Thus the generation of free radicals and oxidative stress can be mediators of tissue injury spasms hands and feet buy tegretol 200mg low price. Leukocytes may play an important role in ischemic disease via formation of microemboli and induction of oxidative damage muscle relaxant shot for back pain tegretol 200mg visa. Activated neutrophils may adhere to other leukocytes and blood cells spasms baby cheap tegretol 100mg free shipping, further narrowing the vessel lumen and muscle relaxant apo 10 tegretol 100mg on line, through release of mediators spasms hamstring buy cheap tegretol 400mg, increasing vessel wall damage spasms calf tegretol 400mg overnight delivery. In one study, P-selectin expression was significantly increased in patients with intermittent claudication and critical ischemia compared to controls. Sequelae are increase in expression of mitochondrial enzymes and accumulation of lactate and acylcarnitines. Kreb Cycle Increased Expression Mitochondrial Enzyme Glucose Fatty Acids Lactate Accumulation Acylcarnitine Accumulation. These steps have been previously identified as targets of oxidative injury in myocardial perfusion-reperfusion models. Supplementation with the antioxidant vitamin C improves endothelial function in patients with diabetes. Muscle Structure and Function in Peripheral Artery Disease In healthy humans, exercise requires coordinated recruitment of appropriate muscle fiber types to meet the demands of specific exercise conditions. There is recruitment of type I oxidative slowtwitch fibers that have high mitochondrial content with low-intensity repetitive contractions. Depending on the exercise intensity of these contractions, the fuel is a balance of fat and carbohydrate oxidation. These fibers have fewer mitochondria than type I fibers and have easy fatigability. These changes reflect a complex combination of changes associated with disuse due to exercise limitation and direct injury from ischemia, ischemia-reperfusion, and chronic inflammatory mechanisms. Patients with claudication also demonstrate extensive skeletal muscle denervation by histological criteria. Denervation injury has been confirmed by electrophysiological testing, and these abnormalities are progressive over time. The neurophysiological changes suggest that the underlying pathophysiology is a distal axonopathy affecting nerve fibers of all sizes. Measures of blood flow in the leg correlate with neurological symptom scores, examination scores, and electrophysiological testing. Increased capillarity may be in compensation for the reduction in large-vessel blood flow, and these changes in peripheral diffusion (higher conductance) may have functional relevance. Whether these gait abnormalities are related to muscle denervation and weakness or are adaptations to minimize development of pain is unknown. Muscle mitochondrial content and mitochondrial enzyme activities reflect the functional state of the individual. Skeletal muscle mitochondrial oxidative enzyme activities increase with exercise training and decrease with prolonged bed rest or inactivity. An increased mitochondrial content might improve oxygen extraction under ischemic conditions and could reflect a compensatory mechanism for any intrinsic abnormality in mitochondrial oxidative capacity. During normal metabolic conditions, fuel substrates such as fatty acids, protein, and carbohydrates are converted to acyl-coenzyme A (CoA) intermediates for oxidative metabolism in the Krebs cycle. Thus, during conditions of metabolic stress, incomplete oxidation or utilization of an acyl-CoA will lead to their accumulation. Transfer of the acyl group to carnitine will result in accumulation of the corresponding acylcarnitine. Importantly, acylcarnitine accumulation may have functional significance in that patients with the greatest accumulation have the most reduced treadmill exercise performance. This limitation in the blood flow response to exercise has metabolic consequences. At the onset of exercise, however, there is a marked delay in systemic uptake of oxygen that parallels a slowed response in skeletal muscle uptake of oxygen. Large-vessel obstruction impairs delivery of oxygenated blood to skeletal muscle during exercise, resulting in a supply/demand mismatch. Arterial hemodynamics and large-vessel blood flow, however, do not fully account for the exercise limitations observed in patients with claudication. Understanding these multiple components of exercise limitation provides insight in to treatment approaches that address the spectrum of abnormalities seen in patients with claudication. Critical limb ischemia is a state characterized by severe impairment of blood flow to the limb whereby the metabolic requirements of the tissue at rest are not met. Multiple occlusive lesions of the limb arteries, coupled with functional and structural changes in the microcirculation, are responsible for inadequate tissue perfusion and formation of skin ulcers and necrosis. Blood components such as red cells, white cells, and platelets aggregate and perturb blood flow in the microcirculation. Dormandy J, Mahir M, Ascady G, et al: Fate of the patient with chronic leg ischaemia. Ciuffetti G, Mercuri M, Mannarino E, et al: Free radical production in peripheral vascular disease. Jansson E, Johansson J, Sylven C, et al: Calf muscle adaptation in intermittent claudication. Creager activity cessation rebalances available blood supply with muscle demand and quickly resolves the pain. Both time of activity to pain onset and time to pain resolution should be consistent and predictable. The distance walked to the onset of leg discomfort is called the initial claudication distance, and the maximal distance the patient can walk without stopping because of leg discomfort is called the absolute claudication distance. Several classification schemes are used to categorize the severity of claudication, including the Fontaine (Table 18-1) and Rutherford classifications (Table 18-2). Patients with pain at rest and with walking had worse functional capacity than those whose pain occurred with walking and stopped with walking cessation, and those who were able to "walk through" the pain. Three quarters of patients with intermittent claudication will have stable symptoms over the next 10 years; approximately 25% will progress to more disabling claudication or critical limb ischemia requiring revascularization or culminating in amputation. This chapter will focus on the history, physical examination, and diagnostic tests important to management of limb atherosclerosis. This includes avid questioning and seeking to elicit historical evidence of limb and systemic atherosclerosis. Clinical suspicion should be heightened in older persons, in those with coronary or cerebral atherosclerosis, and in patients with atherosclerotic risk factors such as diabetes or tobacco use, as well as renal failure (see Chapter 16). Thus, the presence of risk factors for atherosclerosis should lower the threshold for routine screening. Differential Diagnosis of Claudication Once exercise-related discomfort has been established, several alternate vascular and nonvascular diagnoses should be considered (Box 18-1). Vascular disorders include popliteal artery entrapment (see Chapter 62), compartment syndrome, fibromuscular dysplasia, venous insufficiency (see Chapter 55), and vasculitis (see Chapters 41 through 45). Because of an abnormal origin of the medial (or less commonly, lateral) head of the gastrocnemius muscle, the popliteal artery may be compressed with walking and yield symptoms of claudication. Fibromuscular dysplasia is a noninflammatory arterial occlusive disease that most commonly affects the renal and carotid arteries but may involve other arterial beds (see Chapter 63). The word claudication derives from the Latin word claudicatio, which was used to describe the limp gait of a lame horse. As defined in the Rose questionnaire,6 claudication is development of an ischemic muscular pain on exertion. The pain can be characterized as aching, burning, heaviness, feeling leaden, tightness, or cramping. Pain should originate in a muscular bed, such as the calf, thigh, hip, or buttock, and not localize to a joint. The area of the worst blood flow limitation usually subtends the site of muscular discomfort. For example, patients who develop hip or buttock discomfort with walking most likely have distal aorta or iliac artery occlusive disease, whereas patients with calf claudication likely have superficial femoral or popliteal arterial stenoses or occlusions. Patients may complain of leg pain or paresthesias as a result of compression of the lumbar nerve roots from disc herniation or degenerative osteophytes. The paresthesias or pain tend to affect the posterior aspect of the leg and occur with specific positions such as standing or develop at the beginning of ambulation. These symptoms may improve with continued walking or when leaning forward because pressure on the nerve roots is reduced. The pain may be confused with intermittent claudication because it typically occurs with exercise. It can be distinguished from claudication in that the level of activity required to precipitate symptoms varies and does not resolve rapidly with activity cessation. Diabetes is the cause of most nontraumatic lower-extremity amputations in the United States. The pain is often severe and unremitting and localized to the acral portion of the foot or toes, notably at the site of ulceration or gangrene. Blood flow limitation is so severe that the gravitational effects of leg position may affect symptoms. This is typically worse at night when the patient is in bed and the leg, now at heart level, no longer benefits from the dependent position. Placing the foot on the floor beside the bed is a common action used by patients to reduce pain. Inability to use the leg and chronically placing the leg in a dependent position may cause Box 18-1 Nonatherosclerotic Causes of Exertional Leg Pain Nonatherosclerotic arterial disease Atheroembolism Vasculitis Extravascular compression Popliteal artery entrapment Adventitial cysts Fibromuscular dysplasia Endofibrosis of the internal iliac artery Venous claudication Compartment syndrome Lumbar radiculopathy Spinal stenosis Hip/knee arthritis Myositis arteries in the lower extremities may be affected, but the iliac arteries are the most common. It can be diagnosed from the "string of beads" appearance on angiography and by its predilection for the nonbranching points of vessels. Increased calf muscle size with exercise may inhibit venous outflow, cause exertional compartment syndrome-in which tissue pressure is increased and microvascular flow is impeded- and bring about complaints of calf pain or tightness with exertion. Venous claudication may occur as a result of iliofemoral thrombosis with poor collateral vein formation. When venous outflow is impaired, the increase in arterial inflow with exercise increases venous pressure markedly and causes a severe tightness or bursting sensation in the limb. Patients may report improvement in symptoms with leg elevation following exercise cessation. Nonvascular causes of exertional leg pain include lumbar radiculopathy, hip and knee arthritis, and myositis. With severe ischemia, any skin perturbation, including bedclothes or blankets, may cause pain; in ischemic neuropathy, this causes a lancinating pain in the foot. Atheroembolism, or blue toe syndrome, occurs when components of large-vessel atherosclerotic plaque embolize to distal vessels. The embolized material is composed of fibroplatelet debris and cholesterol crystals. A common cause of atheroembolism is iatrogenic disturbance of the vessel, whether from catheterization or surgery. Patients typically have pulses palpable down in to the feet, because the emboli require a patent pathway to distal portions of the extremities. On examination, the patient will have areas of cyanosis or violaceous discoloration of the toes or portions of the feet and areas of livedo reticularis. Acute limb ischemia may occur from thrombosis in situ or from thromboemboli of large fibroplatelet accumulations that originate in the heart or large arteries and occlude conduit arteries (see Chapter 46). These patients have an accelerated course and may present with the "five Ps" of acute ischemia: pain, pallor, poikilothermia, paresthesia, and paralysis. Other causes of ulcers include neuropathy, venous disease, and trauma (see Chapter 61). Nonvascular causes of foot pain include neuropathy, arthritides such as gout, fasciitis, and trauma (see Box 18-1).

I try to send frequent letters to referring physicians to keep them abreast of the progress spasms posterior knee buy 200 mg tegretol fast delivery. It does require time but these letters do not have to be elaborate-just a brief one is fine muscle relaxant voltaren purchase tegretol once a day. The patients must be treated as customers but not made to feel like customers kidney spasms causes buy online tegretol, so it is incumbent upon physicians who manage practices to learn skills never imagined in medical school muscle relaxant johnny english buy cheap tegretol, residency muscle relaxant overdose buy tegretol without prescription, or fellowship spasms right abdomen buy tegretol uk. The specialty is ethically charged to begin with, since its primary focus is on reproduction. While this is not refuted, societal concerns are the means that may be undertaken to produce this offspring. In the traditional sense, the act of reproduction is a private, natural, and conjugal act between two people. However, treatment with the available technologies does everything but meet these criteria. Nevertheless, the right to procreate or reproduce is a liberty that is held sacred by all of us. As caregivers, we must respect this right, yet at same time it is our responsibility to use the available technologies in a responsible manner. I will follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous. I will abstain from whatever is deleterious and mischievous and will not take or knowingly administer any harmful drug. It is complicated in the field of reproductive medicine considering that there can be many participants involved in the treatment. Obviously, we have to look out for the interests of the woman undergoing treatment who is assuming the immediate risks of the treatment and the risks associated with the pregnancy. We also have to protect the rights of her partner who is not exposed to any risks of the treatment but this individual must first desire to become a parent and also be willing to care for any offspring(s) that result from the treatment. As providers, we must also determine the impact of our decisions on the yet unborn child. To further complicate matters, there are other participants to be considered in cases of egg donation and gestational surrogacy. Therefore, before any treatment is started it is imperative that all participants are adequately informed and closely evaluated to ensure that their interests are not compromised as a result of the treatment. To this end, there are four key components that must be in place, including open dialogue, an ethics committee, available resources, and ethical analysis. Open Dialogue When compared to most other medical problems, the treatment of the infertile couple is unique because it can only be accomplished through the coordinated effort of a team made up of physicians, nurses, scientists, mental health professionals, and other key personnel. Each team member interacts with the couple at a different level, which gives each a unique perspective regarding the treatment that is being rendered. Each member must feel comfortable with the treatment that is being performed, otherwise they must be able to voice their concern freely and it must be taken seriously. Ethics Committee Every center should have a committee in place and a forum to discuss ethical issues. The committee can simply include a physician, nurse, mental health professional, and a representative from the laboratory. Depending on the topic that is being discussed, input from an ethicist, lawyer, or member of the clergy may also be helpful. While it is optimal to have periodic committee meetings, it may be necessary to assemble the committee on short notice to resolve an urgent issue. One role of the committee is to review the ethical issues concerning a specific treatment. If a decision is made to offer the treatment, the next step is to develop a comprehensive policy detailing how the treatment will be administered. A final role of the committee is to discuss ethical issues concerning individual cases. Available Resources An important part of an ethical analysis is utilization of available resources. The resources come from the knowledge of individual committee members and from outside resources, as well. They have published reports and statements titled "Ethical Considerations of Assisted Reproductive Technologies" as supplements to the journal Fertility and Sterility. These principles are used when performing a formal ethical analysis and used by the physician in day-to-day patient care. Before an ethical analysis can be performed, one must first have underlying values and the proper perspective. He described virtues that a physician must exhibit to provide ethical care of patients. While these virtues apply to the physician-patient relationship, they are also applicable to all of those who participate in an ethical analysis. Self-effacement: putting aside and not acting on irrelevant differences between oneself and the patient. Therefore, an ethical analysis must be done with compassion, integrity, and devoid of any bias or prejudice. The important ethical principles and concepts that are used to perform an ethical analysis are discussed below. Principle of Respect for Patient Autonomy Patient autonomy is one of the most powerful and prevailing ethical principles. This ethical principle implies that it is the right of the patient to choose his/her treatment and that this choice must be respected. However, it is the obligation of the physician to truthfully inform the patient of the consequences of any action including the benefits, risks, complications, and alternatives. The Principle of Double Effect the principle of double effect is in essence a compromise of two other important ethical principles: beneficence and nonmaleficence. This principle refers to the ultimate goal of any treatment, which is to do something good for the patient. Should we strictly adhere to the nonmaleficence principle, then no treatment would be offered to our patients because there is always the possibility of a bad outcome. The decision to move forward with a treatment occurs when there is a greater balance between good and bad outcomes. While it is important that the harm or risk of any treatment be recognized, the absolute avoidance of harm should not take more importance over the potential benefit of any treatment. Principle of Distributive Justice/Public Stewardship the principle of justice mandates fair and equitable treatment for all. Society has a responsibility to adhere to this principle that is in accordance with support of human dignity and human rights. Therefore, there should be no prejudice in the administration of treatment to the populace and equal access for all. It also applies to the individual physician as well; the physician should not in any way be prejudicial in regard to who is offered treatment and who is not. Paternalism Paternalism refers to the action of a physician who in an authoritative and directive fashion influences the decision-making process. If this action is based on clinical knowledge and absent of any bias or prejudice, it is consistent with the principle of double effect, but at the same time it counters patient autonomy. Standard of Care When examining any therapy, it is important to determine whether this treatment falls within the standard of care for the community. This may hold special importance if this treatment has never been offered-a situation where more critical assessment of all potential outcomes should be discussed before the treatment is offered. However, even if a treatment falls in to the standard of care, it does not necessarily mean that it is guaranteed to be safe. Impact on the Community While any treatment may be ethically sound, it is important to step back and assess the impact of its potential effect on the community. Within any center, there may be staff members who have strong opinions for or against a proposed treatment. For instance, after careful analysis and deliberation, it may be determined that gender selection is ethical. However, if team members are uncomfortable with this procedure, then there should be reconsideration whether to offer gender selection at all or only offer it under certain conditions. The pursuit of human cloning by a small group of scientists several years ago drew worldwide attention. There was public outcry that cloning crosses ethical boundaries and some countries enacted laws against this practice. Case Presentations Case 1 A 35-year-old G0 P0 female presents with a history of infertility. The couple was seen in consultation and they were informed that they had a one in four chance of having a child that would be affected by the disease. Prenatal genetic testing was again discussed but the patient was uncertain if she could undergo a termination of the pregnancy. At this point, it was concluded that the couple had been adequately informed and treatment was offered. This case highlights the important ethical principle of respect for patient autonomy which is founded on informed consent. While it may have been the right decision to offer treatment in this case, if the female and male were carriers of a more severe or fatal disease. Case 2 A 40-year-old G1 P0010 woman presents with a five-year history of unexplained infertility. She was diagnosed with cerebral palsy at birth and is a paraplegic confined to a wheelchair. At another center, she underwent treatment with clomiphene citrate plus intrauterine inseminations, which were unsuccessful. Because of her medical state, she was sent to a high-risk obstetrician for counseling about the risks and complications associated with a future pregnancy. There was added concern that the treatment may result in a multiple pregnancy that could further heighten any risks. During the workup, a hysterosalpingogram confirmed the presence of multiple filling defects in the uterine cavity. The Cystic fibrosis is one of the most commonly inherited diseases in the Caucasian population. It results in thickened mucus production that can alter pulmonary and pancreatic function. During pregnancy, pulmonary hypertension results in a 50% rate of maternal mortality. The patient was seen in consult and the implications of her condition were discussed. However, she was not concerned and stated that "I am a survivor and always beat the odds. A decision was made by the physician not to treat this patient based on medical reasons and the high likelihood of a bad outcome during a future pregnancy-maternal death. This case illustrates an example of paternalism and how it influenced the decision not to move forward. The decision not to treat this patient was done in an unbiased fashion and was based on medical fact. It was determined that the severity of a bad outcome as a result of the treatment far outweighed the benefit of the treatment-the principle of double effect. Case 3 A 40-year-old G1 P1 woman presents with her husband with unexplained infertility. The couple has one daughter and they inquired about gender selection in their quest for a male offspring. In addition, a visit with a social worker is mandatory and the couple had to agree to transfer embryos of the undesired gender if they were the only ones available. The topic was never brought up again by the couple and they underwent several cycles of insemination treatments that were unsuccessful. The couple presented for the embryo transfer; when they found out that both embryos were female, they chose to forego the transfer and discard the embryos. Over a decade ago, sperm-washing techniques were developed to select out the X or Y bearing sperm. In retrospect, all of these techniques did little to help the couple achieve their goal. However, there is ongoing debate as to whether gender selection is an ethical practice. At one end of the spectrum is the couple who presents stating that they have three sons at home and would like to have a female offspring balancing the family. They would also transfer embryos of the undesired gender if they were the only ones available. This is a situation that many would agree is an acceptable one to consider gender selection. This is obviously a situation where many clinicians would feel uncomfortable in proceeding with the request. Initially we were concerned about whether offering gender selection was an ethical practice and we elected not to offer this option to couples. Further, if only embryos of the undesired sex were available, then it was requested that the couple agree to transfer them. Presently, we have modified the policy once again such that any couple (fertile or infertile) can undergo gender selection for the purposes of family balancing or for their first born.

Without guidance from the physician spasms youtube purchase tegretol no prescription, some patients become sedentary in response to uncomfortable or heavy sensations in the affected limb muscle relaxant brand names cheap tegretol 100mg with visa. Reduced physical activity at work and home leads to apathy and malaise; that consequence can be averted by encouraging physical activity with proper support hose muscle relaxant at walgreens buy online tegretol. Regular exercise appears to reduce lymphedema as long as elastic support (or hydrostatic pressure) is applied back spasms 39 weeks pregnant tegretol 200 mg otc. Swimming is a particularly good physical activity for these patients because the hydrostatic pressure of the surrounding water negates the need for compressive support muscle relaxant injection order tegretol now. Although the elements of decongestive lymphatic therapy were initially derived empirically muscle relaxant generic buy discount tegretol on-line, the efficacy of these interventions has now been demonstrated in numerous prospective observations. Multichamber pneumatic devices are available that intermittently compress the limb; techniques that employ sequential graduated compression (in which the cuffs are inflated sequentially from distal to proximal sites with a pressure gradient from the most distal cuff to the most proximal) are the most efficacious. Consequently, as fluid shifts occur during pneumatic compression, the root of the limb must be decompressed with the aforementioned manual techniques. Even then, successful drainage is gained in only about 50% of cases and is often temporary. In theory, if the lymphatic vessels in the flap remain functional, they eventually may anastomose with the surrounding lymphatics and provide an alternative pathway for drainage from the edematous area. The myocutaneous flap (using latissimus dorsi) has been reported to be useful for the upper extremity, and the intestinal flap (enteromesenteric bridge) may improve drainage in the lower extremity. One of the latest techniques involves harvesting normal autogenous lymphatic vessels for use as bypass grafts around a lymphatic obstruction. All these microsurgical techniques require the presence of dilated lymphatic vessels distal to the obstruction. These operations obviously are of no value when the lymphatic obstruction is at the level of the smaller distal vessels. The argument has been made, however, that lymphatic bypass operations should be performed as soon as possible after the onset of obstruction to avoid the cutaneous changes of chronic lymphedema, as well as the gradual destruction of the distal lymphatic channels. An appropriate candidate for such surgery would be an individual with a recent onset of lymphedema secondary to trauma and with an otherwise normal lymphatic system proximal and distal to the area of obstruction. In a recently published large series of such appropriately selected patients, microsurgical lymphatic-venous anastomosis accomplished objective reduction of limb volume in 85% of cases. Reduction procedures involve resection of a portion of the skin and subcutaneous tissue and subsequent closure of the wound to reduce the limb diameter. Acute complications include wound infection or necrosis of the skin flaps; late complications include recurrent cellulitis or verrucous hyperplasia of the skin grafts. Swelling of the extremity is more likely to progress if recurrent bouts of cellulitis are not adequately controlled or if adequate compressive support is not provided postoperatively (the procedure does not correct the obstruction to lymph efflux). These limbs require lifelong compressive support and, because of their vulnerability to infection, fastidious attention to hygiene. Some of the most challenging patients cared for by a lymphedema center are those who have had aggressive reduction surgery, producing a painful mutilated limb that is immunocompromised and ravaged by recurrent fungal and bacterial infections. Currently, medical therapy is directed at preventing complications and retarding progression of the disorder, whereas surgery is palliative. Of interest are recent reports of therapeutic success of liposuction in advanced stable lymphedema. Surgical liposuction of chronic postmastectomy lymphedema has been reported to produce excellent results, with sustained reduction of excess volume. In one series, an average long-term reduction of edema volume of 106% was observed in 28 patients with an average edema volume of 1845 mL. However, the volume reduction is unsuccessful unless compression therapy is maintained after the surgical intervention. For these reasons, there has been emphasis on the possible application of effective molecular therapies. Among these, the most exciting to date is therapeutic lymphangiogenesis, which is based on insights in to the developmental biology of the lymphatics. It is believed that the mutant form of the receptor is excessively stable as well as inactive, so the normal signaling mechanism is blunted, leading to hypoplastic development of the lymphatic vessels. Intensive future investigation is necessary to verify the therapeutic potential of such approaches, as well as to establish doseresponse relationships and durability of the therapeutic response. As with other forms of angiogenic therapy, the relative virtues of growth factor (gene product) therapy versus gene therapy must be established. These mixed vascular deformities are best characterized by the dominant vascular anomaly, whether angiomatous, venous, or arteriovenous. It is a congenital disorder in which varicose veins, cutaneous nevi, and limb hypertrophy are observed. It has been suggested that this syndrome reflects a generalized disturbance of mesodermal development, thereby engendering the commonly associated anomalies: bony overgrowth, soft-tissue hypertrophy, syndactyly, hypospadias, and lymphatic hypoplasia. The condition can be ascribed at least in part to concomitant dilated tortuous lymphatics and consequent lymphedema. The pathophysiology of this disorder likely reflects the enormous increase in blood flow consequent to multiple arteriovenous fistulae; this increase in capillary filtration would then lead to an increase in lymphatic load, producing first vascular dilatation and, ultimately, insufficiency. Lymph reflux in the limb may lead to the appearance of lymph vesicles in the skin, which should be treated conservatively. Associated lymphangiectasia can be observed in numerous additional organs including liver, kidney, testes, lymph nodes, adrenals, and intestines. When chylothorax is present, repeated thoracentesis and pleurodesis is often required. In one small series, all patients died within 6 to 33 months of clinical presentation. The vast majority of such lesions have been observed in lymphedema patients that are breast cancer survivors with chronic significant edema. Whatever the clinical substrate, the prognosis for survival is poor, even following radical amputation. The presence of chylous lymph denotes incompetence of lymphatic flow that extends to the level of the lacteals, at the point where they join the preaortic lymphatics and the cisterna chyli. In the former case, hypoplastic or dilated incompetent lymphatics reflect the inherited defect of lymphatic development; in secondary forms, thoracic duct obstruction occurs through surgical mishap, trauma, malignancy, or the damage created by filariasis. The abnormal fluid drains directly from vesicles on the surface of the leg or on the genitalia. Variants of this same presentation can produce chylothorax, chylous ascites, chylous arthritis, and chyluria. In general, if chyle is present in the refluxing body fluid, the therapeutic approach should include a fat-restricted diet with supplementation of medium-chain triglycerides. If the response is not satisfactory, complete elimination of chyle from the fluid can be accomplished at least temporarily with total parenteral nutrition. The natural history of reflux reflects the tendency for the condition to worsen with the passage of time. In some patients, there may be an episodic pattern of leakage with sudden exacerbations. In patients with the secondary form, an assiduous search for predisposing malignancy or extrinsic lymphatic obstruction should always be undertaken. In patients with the various forms of visceral involvement, complex surgical interventions are sometimes required to mitigate the functional and symptomatic consequences of reflux in to the serous cavities. Rather, these lesions are composed of profuse numbers of dilated thin-walled lymphatic vascular structures. They can occur throughout the body, but are seen most commonly on the proximal extremities and at the limb girdle. Small clear vesicles are observed in the skin, sometimes with associated cutaneous bleeding. The cavernous lesions are typically found in the mouth, mesentery, and on the extremities; cystic hygromas present in the neck, axilla, and groin. When chyle refluxes back in to the villi as a consequence of the effective blockade of its passage in to the central lymphatics, this condition engenders weight loss, diarrhea, and steatorrhea as protein, fat, calcium, and fat-soluble vitamins are malabsorbed. In addition to the secondary forms of lymphatic obstruction (usually malignant), the primary hypoplastic and lymphangiectatic disorders can also predispose to enteropathy; in these cases, lymphedema of an extremity often precedes or accompanies the appearance of the enteropathy. As with other forms of reflux, the initial therapeutic strategy should entail medium-chain triglyceride supplementation, with restriction of total dietary fat intake. Where the response to conservative therapy is insufficient, it has been suggested that systemic treatment with octreotide may help alleviate the severity of the disorder, although the mechanism of benefit is not entirely understood. Bockarie M, Tisch D, Kastens W, et al: Mass treatment to eliminate filariasis in Papua, New Guinea, N Engl J Med 347:1841, 2002. Szuba A, Rockson S: Lymphedema: a review of diagnostic techniques and therapeutic options, Vasc Med 3:145, 1998. Hojris I, Andersen J, Overgaard M, et al: Late treatment-related morbidity in breast cancer patients randomized to postmastectomy radiotherapy and systemic treatment versus systemic treatment alone, Acta Oncol 39:355, 2000. Tengrup I, Tennval-Nittby L, Christiansson I, et al: Arm morbidity after breast-conserving therapy for breast cancer, Acta Oncol 39:393, 2000. Werngren-Elgstrom M, Lidman D: Lymphoedema of the lower extremities after surgery and radiotherapy for cancer of the cervix, Scand J Plast Reconstr Surg Hand Surg 28:289, 1994. Nagai Y, Aoyama K, Endo Y, et al: Lymphedema of the extremities developed as the initial manifestation of rheumatoid arthritis, Eur J Dermatol 17:175, 2007. Stemmer R: Ein klinisches Zeichen zur fruh-und differential-Diagnose des Lymphodems. Brorson H, Ohlin K, Olsson G, et al: Breast cancer-related chronic arm lymphedema is associated with excess adipose and muscle tissue, Lymphat Res Biol 7:3, 2009. Mallon E, Powell S, Mortimer P, et al: Evidence for altered cell-mediated immunity in postmastectomy lymphoedema, Br J Dermatol 137:928, 1997. Servelle M: Surgical treatment of lymphedema: a report on 652 cases, Surgery 101:485, 1987. Vaqueiro M, et al: Lymphoscintigraphy in lymphedema: an aid to microsurgery, J Nucl Med 27:1125, 1986. Matsushima S, Ichiba N, Hayashi D, et al: Nonenhanced magnetic resonance lymphoductography: visualization of lymphatic system of the trunk on 3-dimensional heavily T2-weighted image with 2-dimensional prospective acquisition and correction, J Comput Assist Tomogr 31:299, 2007. Gniadecka M: Localization of dermal edema in lipodermatosclerosis, lymphedema, and cardiac insufficiency: high-frequency ultrasound examination of intradermal echogenicity, J Am Acad Dermatol 35:37, 1996. Kubik S: the role of the lateral upper arm bundle and the lymphatic watersheds in the formation of collateral pathways in lymphedema, Acta Biol Acad Sci Hung 31:191, 1980. Baldwin M, Stacker S, Achen M: Molecular control of lymphangiogenesis, Bioessays 24:1030, 2002. Leduc O, Leduc A, Bourgeois P, et al: the physical treatment of upper limb edema, Cancer 83:2835, 1998. Ogawa Y, Yoshizumi M, Kitagawa T, et al: Investigation of the mechanism of lymphocyte injection therapy in treatment of lymphedema with special emphasis on cell adhesion molecule (L-selectin), Lymphology 32:151, 1999. Campisi C, Boccardo F: Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery, World J Surg 28:609, 2004. Veikkola T, Karkkainen M, Claesson-Welsh L, et al: Regulation of angiogenesis via vascular endothelial growth factor receptors, Cancer Res 60:203, 2000. Enholm B, Karpanen T, Jeltsch M, et al: Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin, Circ Res 88:623, 2001. Ramani P, Shah A: Lymphangiomatosis: histologic and immunohistochemical analysis of four cases, Am J Surg Pathol 17:329, 1993. Tibballs J, So to R, Bharucha T: Management of newborn lymphangiectasia and chylothorax after cardiac surgery with octreotide infusion, Ann Thorac Surg 77:2213, 2004. Plummer the most widely accepted classification of arterial infections was introduced by Wilson et al. A preestablished aneurysm that became infected as a result of bacteremia is classified as an infected aneurysm. Traumatic infected aneurysms include infected aneurysms due to trauma or iatrogenic injury. Contiguous arterial infection is due to direct extension of an adjacent infection in to the wall of the artery, such as infected aortitis associated with vertebral osteomyelitis. The specific classification based on etiology will be acknowledged wherever appropriate in this chapter. However, for purposes of clarity and simplification, the generic term infected aneurysm will be applied to include all arterial infections discussed. In the pre-antibiotic era, 86% of patients with arterial infections had evidence of endocarditis. In 1984, Brown and associates reported a collective series of infected aneurysms based on a search of the English literature. The authors separated the reported experience in to cases occurring before 1965 and those occurring since that time. Accuracy of the results suffers because of important differences in diagnosis and reporting frequency between the two periods. Nevertheless, this collective experience remains the largest comparative analysis of infected aneurysms to date. In the earlier part of the series, endocarditis was still the leading cause of infected aneurysms, but arterial trauma of all types became the leading cause after 1965. The authors attributed this etiological shift to a substantial change in the pattern of antibiotic use for treatment of sepsis and trauma. The increase in interventional procedures was particularly notable after the pioneering work of Grunzig and others in the 1970s. The enthusiasm for endovascular technology seen in recent years suggests that arterial trauma may soon become an even more important cause of arterial infection. Vascular infection is a rare but serious problem associated with potentially disastrous complications.

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The period of aortic occlusion is minimal and accounts for the lower incidence of intraoperative hemodynamic and metabolic stress compared with patients undergoing open surgery spasms after gall bladder removal 400mg tegretol amex. Some of the initial approaches involved techniques similar in some fashion to modern endovascular techniques spasms during bowel movement buy tegretol in united states online. Early techniques ranged from simple aortic ligation to aortic wrapping with cellophane muscle relaxant injections neck buy tegretol online now. In 1951 muscle relaxer zoloft order tegretol canada, the first replacement of an aortic aneurysm with an aortic homograft was described by Dubost et al muscle relaxant benzo purchase cheap tegretol on-line. Although excellent results have been obtained with conventional aneurysm repair muscle relaxant safe in pregnancy purchase discount tegretol on-line, it remains a complex, challenging operation that initiates great physiological stress for patients. This approach allowed for intraluminal exclusion of an aneurysm with placement, through the femoral arteries, of an endograft. The hope was that this would decrease the morbidity and mortality of aneurysm repair and allow repairs to be performed in patients with significant comorbidities. The original endograft was constructed of a Dacron tube sutured to a Palmaz stent. Several generations of endografts have since been developed, tested, and put in to general clinical use. Our understanding of the complexities of this mode of treatment is only just being realized and examined. This chapter reviews what is currently understood about endograft repairs of abdominal aortic aneurysms. Anatomical Requirements the exact anatomical requirements for placing an aortic endograft vary with device design. There are key aspects of each device and aortic anatomy to be aware of when assessing a patient as a potential candidate for endograft repair. Preprocedural imaging is paramount for proper assessment of proximal and distal sites of fixation, as well as the path the endograft will traverse before taking its postdeployment position. Imaging Successful endograft placement is completely dependent on adequate and accurate preoperative planning. Preprocedural imaging allows the surgeon to determine whether a patient is an acceptable candidate for endovascular aortic grafting and which device is best suited for a particular patient; this ultimately allows for determining the proper size of the endograft. Preoperative angiography is now rarely employed and reserved for cases where an adjunctive therapeutic intervention. The axial images may "cut" vessels at an angle, particularly iliac arteries that have some degree of tortuosity, thus creating an ellipse as opposed to visualization of the true lumen diameter. The classic teaching is that rupture rates for aneurysms depend on the size of the aneurysm. Rupture rates of 5% to 7% per year are estimated for aneurysms between 5 and 7 cm in diameter, and a greater than 20% rupture rate per year is estimated for larger aneurysms. Its usefulness, however, is often limited by availability and physician expertise. Magnetic resonance imaging may provide a useful modality to avoid use of iodinated contrast agents in patients. It is an invasive procedure, often performed at the time of angiography Images produced by. Unless the catheter remains centerline within the aorta, the images produced will be elliptical, which may also provide shorter-thanrequired length measurements. Its primary use is at the time of stent graft placement to assess graft position relative to the renal artery ostia; this can help diminish the amount of contrast agent required. Several devices employ the use of a suprarenal uncovered (or bare) stent to provide additional protection against graft migration. Suprarenal stent fixation may be useful, particularly in patients who have a shorter aortic neck, because it transfers protection against migration to a more normal segment of aorta. The suprarenal stent, however, does not provide any function with regard to creating a circumferential seal. In addition to the length of the neck, other anatomical characteristics are important when determining whether patients are suitable candidates for endovascular aneurysm repair. These include aortic neck angulation, the shape of the neck, and the quality of the neck. Neck angulation refers to an alteration in the direction the aorta takes with regard to the centerline pathway. Aortic neck angulation of greater than 60 degrees compared to the centerline is often considered prohibitive for endovascular aneurysm repair. The shape of the aortic neck also affects the ability of the graft to obtain a seal as well as fixation. First, it is the site of proximal fixation that will prevent the device from migrating distally. Second, a circumferential seal must be obtained between the graft and the aorta in this area to prevent leakage of blood in to the aneurysm sac. The exact length of aortic neck required is somewhat device dependent, but most commercially available devices require a 10- to 15-mm length of aortic neck Iliac Arteries the iliofemoral arterial system is important in endograft placement for two reasons. Iliac artery diameter and tortuosity can adversely affect the ease with which the endograft traverses this course. Certainly the presence of significant atherosclerotic disease can cause arterial narrowing that inhibits placement of the device. Second, the iliofemoral system is important because it is the site of the distal seal between the endograft and the iliac artery, preventing retrograde flow of blood in to the aneurysm sac. D1 represents diameter at proximal aspect of aortic neck, and D2 represents diameter at distal aspect of aortic neck. Distance between D1 and D2, in general, must be 10-15 mm to adequately place an endograft. The ideal delivery system easily traverses these arteries on the basis of an intrinsic degree of flexibility. Again, different delivery systems have different abilities to track through tortuous iliac arteries, and some may be more successfully placed than others in this anatomical variant. Delivery systems composed of long, flexible, tapered tips pass more easily than those with short, stiff, blunt tips. Degree of tortuosity may be underestimated in direct anterior-posterior view, but on a more oblique angle (B), a more significant degree of tortuosity is visible. Many of the features necessary for an adequate aortic neck are also necessary for the distal landing zone. Presence of thrombus, calcification, and tortuosity can significantly hinder the iliac limb seal. Ectatic or aneurysmal iliac arteries obviously affect the ability of the graft to seal against the iliac limb. Most available endograft systems require at least a 15-mm segment of iliac artery to be of adequate caliber and free of significant disease to obtain a distal seal. If this is not present, adjunct interventions can be performed to assist in placing the device. A number of features have been noted to affect the deliverability of endograft devices. As stated previously, long, flexible, tapered tips pass more easily than short, blunt, stiff ones. This allows for easier maneuverability through tortuous vessels, as well as past sites of narrowing. Larger-caliber devices are also more difficult to deliver, particularly in patients with smaller-diameter arteries. This can greatly affect placement of specific endografts in specific anatomical variants. The complexity of the delivery system also affects the ease with which it is placed. Some devices generally provide a simple maneuver to deploy the graft, whereas others have several complicated steps. Endograft Features the ideal endograft should be flexible enough to maneuver through tortuous and angulated vessels but also rigid enough to prevent kinking. It should have a low profile (having a small external diameter) that would allow it to be placed through as small an arteriotomy as possible. Although this decreases the risk of endoleaks at the graft-graft interface, the unibody design often requires a larger delivery system, and sizing can be more difficult. Generally there is a main body that may have one attached limb and one or two docking limbs. These devices can be introduced through smaller delivery systems and offer a greater degree of flexibility with regard to placement. With multiple sites of graft-graft interface, however, there is an increased risk of endoleak, as explained later. The graft material is typically supported by a metal framework that is commonly stainless steel, its modified version Elgiloy, or nitinol. The graft support can be placed inside the graft material (endoskeleton) or outside the graft (exoskeleton). Grafts can be fully supported, having stent material throughout, or only partially supported, with aspects of the device composed only of graft material and no metal. These stents provide some degree of radial force that helps provide a seal, as well as providing a point of fixation. Some devices have hooks or barbs in the proximal aspect of the skeleton that help anchor the graft on to the aortic wall and prevent migration. In addition, some devices employ a metal framework that extends above the fabric and is used to engage the aorta in the pararenal or suprarenal location. The second function of the skeleton is to provide columnar strength, which may prevent graft migration. The skeleton can also prevent kinking and occlusion of limbs as they traverse the aortoiliac anatomy. Lack of stents, however, may allow a graft to adapt more readily to morphological changes without dislocation of attachment sites. The interplay of the stent and fabric materials can lead to eventual erosion of the fabric. Endograft Design Endograft design can greatly affect the ability of the device to be placed in patients, particularly in those with complex anatomy. The ability to deliver the endograft safely and effectively in this fashion is a prerequisite for effective repair. Inadequate diameter or presence of extensive calcifications can exclude standard endograft placement. It is intuitive that the size of the delivery system cannot be larger than the size of the iliac arteries it traverses. Most sheaths are sized based on inner diameter, so knowledge of the outer diameter of the sheaths is necessary for safe graft placement. Most delivery systems easily traverse an iliofemoral segment of 7 to 8 mm in diameter (or a sheath that does not exceed 21 F), although several designs that provide a lowerprofile system are currently in clinical trials in the United States. Specific Grafts Various endografts are currently commercially available or in clinical trials in the United States. Graft Placement and Postoperative Management Once the patient is deemed an endograft candidate, the best graft has been chosen, and the device properly sized, the patient can undergo implantation. The majority of endografts are placed through the femoral arteries that have been operatively exposed. The majority of surgeons prefer the use of the transverse incision as it associated with a lower rate of wound complications (12. Suture-mediated closure devices facilitate this process, and using a "preclose" technique has been described to allow closure of sheaths as large as 24 F 27 Use of this procedure has. Prospective analysis has demonstrated that use of a percutaneous approach may shorten operating times and reduce the rate of wound-related complications, without a significant increase in overall procedural cost. Small boluses of contrast agent are delivered to further define the anatomy and localize the renal arteries. With an angulated aorta, it is important to remember that the best view of the renal arteries and visualization of the fixation zone may not be in a direct anterior-posterior plane but at a more cranialcaudal angle. The device is then generally advanced over a stiff guidewire and correctly positioned to allow the most extensive coverage within the aortic neck without intruding on the orifice of the renal arteries. Once the main body and ipsilateral limb have been placed, the contralateral limb has to be placed. The sequence of events for this varies depending on graft design-whether unibody or modular. Return to activities of daily living has been shown to be quicker following endovascular repair than open surgery. Anatomical changes in the native vessel, particularly at the proximal neck, can cause conformational changes in the implanted device that mandate close follow-up. In addition, late failures have been identified that have required reintervention. Based on these findings, the group recommended that surveillance should be directed toward those patients identified as having a high risk for postoperative complications. It is widely available, has rapid data acquisition, reproducibility, and is uniform across institutions. The major concerns associated with this modality are use of a contrast agent and the potential associated nephrotoxicity, radiation exposure, and cost. It is considered the gold standard for assessing aortic diameter, with nearly 100% sensitivity and specificity. Use of arterial phase alone has a lower diagnostic value than combined arterial and delayed-phase scanning. Repetitive use of iodinated contrast can have a cumulative deleterious effect on renal function, especially in the elderly and those patients with preexisting renal impairment. Furthermore, there is a risk of nephrogenic systemic fibrosis associated with gadolinium contrast use in patients with renal insufficiency.