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Phagocytosis of debris by macrophages may serve as a stimulus for cellular activation with synthesis and secretion of bone-resorbing factors finasteride 5mg generic. Such factors include proinflammatory mediators interleukin-1 (IL-1) [28 cheap 1 mg finasteride free shipping,29] cheap 5 mg finasteride with mastercard, interleukin-4 (IL-4), interleukin-6 (IL-6) [28,29,31], interleukin-8 (IL-8), gran- ulocyte macrophage colony stimulating factor (GM-CSF), tumor necrosis factor- (TNF. Interleukin-4 was found to down-regulate particle-induced activation of macrophages, whereas titanium particles up-regulated the expression of matrix metallo- proteinases stromelysin and collagenase in fibroblasts. Nitric oxide and cyclooxygenase 2 (COX-2) play important roles in wear debris. Thus, nitric oxide production at titanium surface was not detected in one study. Release of selected chemokines (MCP-1, MIP- 1 , and RANTES) was found to initiate macrophage accumulation around wear debris. Macrophage subgroups interact differently to polyethylene and titanium implants. Macrophages positive for ED-1 are involved in the tissue response of polyethylene and titanium. Chemo- kines and cytokines mediate inflammation. Mononuclear osteoclast precursors, stimulated by monocyte colony stimulating factor (M-CSF), initiate osteoclastic activity, and bone resorp- tion begins. One article also demonstrated that even osteoblasts that become positive for macro- phage marker CD68 might play a role in periprosthetic bone resorption. Osteoblasts present phenotypic differentiation depending on the chemical composition of the debris particles. Particles are usually found in the cytosol of the cells following phagocytosis. Osteoblasts present extensive ruffled cell membranes, less developed endoplasmic reticulum, swollen mitochondria, and vacuolar inclusions. Metallic particles and their side effects are not only limited to the peri-implant site; they are also found in other organs, such as the peripheral blood, liver, spleen, and lymph nodes. Metallic particles in the liver or spleen were more prevalent in patients who had had a 4 Korkusuz and Korkusuz Figure 1 Metal implant–hard tissue interface and the biomaterial-initiated osteolytic and/or adaptive cascade. In one living patient, dissemination of titanium particles from a hip prosthesis with mechanical failure was associated with visceral granulomatosis reaction and hepatospleno- megaly, which required operative and medical treatment [41,42]. Even in well-functioning prostheses the serum and urine concentrations of titanium and chromium were found to be higher than in the normal population. Serum levels of bone-resorbing cytokine GM-CSF level Hard Tissue–Biomaterial Interactions 5 increased significantly in patients with aseptic loosening of hip prostheses. Patients having revision arthroplasty of the hip presented increased chromosome translocations and aneuploidy in their peripheral blood. Although intraarticular testing of titanium and chromium alloys in rats revealed no local tumor development a study of 12 cases on orthopedic implant–related sarcoma revealed using metallic implants as artificial joints might lead to severe end results. Two of the high-grade sarcoma of Keel’s study were located in the soft tissue and 10 in bone. Seven patients were reported to develop osteosarcoma, four malignant fibrous histiocytoma, and one a malignant peripheral nerve sheath tumor. Alloys that contain nickel had higher carcinogenic and toxic potencies. One important aspect of sarcoma arising from artificial joints is the differential diagnosis of infection. Chronic and long-lasting infections may trigger sarcoma. Aggressiveness, high-grade, and metastasis of sarcoma arising from artificial joints need precaution and awareness of the symptoms. Further studies related with this severe complication are essential. It is recommended that surgeons should (1) select prostheses with minimal susceptibility to metal corrosion and wear, (2) replace implanted prostheses when there is evidence of corrosion and mechanical failure, (3) carry out epidemiological studies to quantify cancer risk in patients with various types of metal implants, and (4) improve in vitro assays for carcinogenicity of alloys intended for use in bone tissue. Effectiveness of Metal Coatings Coatings or ion implantation [49–51] are usually used to improve the biocompatibility of im- plants and decrease metallic wear and corrosion. Rough or porous surfaces allow cell attachment.

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However 1mg finasteride sale, it is important to perform adequate history taking and physical examination so that conditions that should be promptly referred to another specialist order finasteride 1mg, for instance discount finasteride 1mg amex, a neurologist, are identified. Although it is beyond the scope of this chapter to address the full scope of disorders that could result in visual disturbance, many of the char- acteristic disorders are identified. The definitive diagnostic studies are not performed at a general practice site, but rather are performed by a specialist to whom the patient is referred. These include dilation of the eye, intraocular pressure measurement, magnification, etc. CATARACTS Cataracts are opacities of the optic lens and most typically occur as a disease of aging. However, cataracts can be caused or accelerated by certain conditions, including exposure to ultraviolet light and to certain drugs as well as by such systemic diseases as diabetes. The patient with cataract generally complains of a progressive decrease in visual acuity that is painless. The altered vision includes general blurring and haziness of vision, as well as the development of halos and glares in response to bright lights, as when driving in the dark. The opacities may be visible as gray or whitening areas over the pupil. The opacity makes ophthalmologic examination difficult, obscuring the visualization of the posterior chamber and retinal structures. Early cataracts are best detected through ophthalmic exam of dilated eye, using magni- fication. CHRONIC OPEN-ANGLE GLAUCOMA Glaucoma is the condition in which an increased intraocular pressure results in neu- ropathy of the optic nerve. This most common form of glaucoma results in a gradual and progressive altered vision. Certain individuals have a higher incidence of chronic glaucoma, among them, African Americans, diabetics, and those over 35 years of age, particularly if they have a positive family history. Patients with chronic open-angle glaucoma generally have no complaints other than altered vision. The disease may progress before the patient perceives the decreased vision. The visual disturbance progresses from blurring to complete vision loss, if not recognized and treated. The patient may have required frequent corrective prescription changes up until definitive diagnosis. The vision loss begins peripherally, so that central vision is not lost until late in the disorder. The physical examination identifies an increased cup-to-disk ratio. A normal tonometric value is under 21, although the value can vary or fluctuate. Tonometry must be considered in combination with retinal signs of glaucoma and visual fields. Ophthalmologists can perform additional tests, including gonioscopy, which assesses the drainage angle, to determine whether it is open or closed. ACUTE CLOSED-ANGLE GLAUCOMA This less-common form of glaucoma results in acute visual disturbance. The increased intraocular pressure may be transient, triggered by conditions that cause pupillary dilata- Copyright © 2006 F. As the intraocular pressure acutely increases, the patient typ- ically experiences considerable symptoms, although they may resolve before the patient arrives for evaluation. It is very important that the examiner not dilate the eyes when a patient presents with a history of unilateral eye pain and visual disturbance because the dilation may further exacerbate the intraocular pressure increase.

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Local inoculation of organisms into the joint space is the most com- mon route of acquisition B purchase finasteride 5 mg with visa. The finger joints are the most commonly involved site E generic finasteride 1mg on line. Most cases are polyarticular Key Concept/Objective: To understand the epidemiology and pathogenesis of bacterial arthritis 48 BOARD REVIEW Patients with underlying joint damage from any cause (e buy finasteride 5mg amex. In the majority of cases, bacte- ria are presumed to reach the joint space via the bloodstream rather than by direct inoc- ulation (as would occur with postarthroplasty infections or with infections associated with trauma). The knee and hip are the most commonly involved joints; bacterial arthritis of the small finger joints is uncommon. Only 10% to 15% of cases of septic arthritis are polyarticular. HIV infection has not been identified as a risk factor for sep- tic arthritis. A 23-year-old sexually active woman presents with left knee and wrist pain. She initially experienced polyarthralgias and low-grade fevers for several days, after which she developed progressive left knee pain. On examination, she is febrile and has a significant effusion and pain with passive range of motion of the left knee. A few scattered necrotic pustular lesions are present on the extremities. The rest of the examination (including pelvic examination) is negative. Appropriate cultures are obtained, and a diagnostic aspirate of the knee joint reveals a WBC count of 45,000/mm3 (predominantly polymorphonuclear leukocytes), but the Gram stain is negative. Cultures of the joint fluid eventually yield Neisseria gonorrhoeae. Which of the following statements about gonococcal arthritis is true? Arthritis caused by this organism is more common in men than in women B. Progressive joint damage leading to permanent disability is likely C. Absence of clinical pelvic gonococcal infection rules out the diagnosis D. The synovial fluid usually tests positive on Gram staining E. The prognosis for patients with gonococcal arthritis is generally better than for patients with nongonococcal arthritis Key Concept/Objective: To be able to recognize the clinical features of gonococcal arthritis Gonococcal arthritis is a relatively common cause of septic arthritis in young, otherwise healthy, sexually active patients. Skin rash (scat- tered pustular skin lesions), migratory polyarthralgias/polyarthritis, and tenosynovitis constitute the classic triad of disseminated gonococcal infection. The distinction between gonococcal and nongonococcal arthritis is clinically useful, because gonococ- cal infections tend to have a better prognosis than nongonococcal arthritis. Progressive joint damage is uncommon in gonococcal arthritis. Diagnosis can be difficult, and the results of Gram staining of synovial fluid are usually negative. The frequency of posi- tive cultures taken from various sites of infection is as follows: urogenital, 86%; synovial fluid, 44%; rectal, 86%; and pharyngeal, 7%. In order to maximize the diagnostic yield, it is important to obtain cultures from all sites of potential exposure (e. Although genitourinary infection is present in the majority of patients, it may be asymptomatic in women. What is the best treatment for the patient described in Question 76? Cefazolin alone Key Concept/Objective: To know the appropriate management of gonococcal arthritis Up to one third of gonococcal isolates in the United States are resistant to penicillin or tetracycline; these agents are therefore not recommended for treatment of gonococcal 7 INFECTIOUS DISEASE 49 infection. Parenteral regimens of ceftriaxone, cefotaxime, or imipenem are recom- mended.

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We also know that unnecessary nongraduated elastic stockings are one of the causes of superficial cellulite due to compression and the slow- ing of microcirculation (11) cheap finasteride 5 mg online. We know that three forms of edema can be associated with cellulite disorder: venous edema generic 1 mg finasteride otc, lymphatic edema buy discount finasteride 1mg on-line, and lipedema. Venous edema is basically characterized by a release of kinins, toxic substances, and iron that carries calcium with it. It is an edema associated with phlogosis of the tissues and deposition of hemosiderin. Lymphedema is a pathological condition characterized by a state of tumescence of the soft tissues, usually superficial, due to accumulation by stasis of high protein-content lymph caused by primary and/or secondary alterations of the lymphatic vessels. Lym- phatic edema is linked to alterations of the lymphatic vessels, and is characterized by free water in the interstices that has bonded with proteins and solutes, forming an edema of lymph with interstitial hyperpressure (12). Lipedema is a particular syndrome characterized by subcutaneous deposition of fatty tissue and water, especially in the buttocks and lower limbs, which may or may not be associated with lymphedema and/or lipodystrophy (13,14). It is an edema characterized by an increase of free water in the interstices; it is not lymph—it is free water and fatty tissue. LYMPHEDEMA Lymphedema is a chronic and progressive affliction that is very difficult to cure. The aim of treatment is to keep the disease stable in order for the patient to live normally. In this type of pathology, the first component is edema and the second is fibrosis. The increase of protein levels in the tissues contributes to the development of edema and probably causes chronic inflammation and subsequently the fibrosis. ANATOMY OF CELLULITE AND THE INTERSTITIAL MATRIX & 31 The basic clinical sign of lymphatic problems, either mechanical or dynamic, is a cold and pale swelling, which is initially viscous and later hardens but is not painful in most cases. With the increase in severity of edema, there is an increase in limb volume. At this point, it is not sufficient to hold the limb in an elevated position in order to reduce edema; fibrosis is already present. LIPEDEMA AND LIPOLYMPHEDEMA Lymphedema is described as a pathology characterized by a tumescent state of soft tissues, usually superficial (15), and is related to an accumulation of lymph with high protein con- tent due to stasis in the interstitial space. It is determined by primary and/or secondary damage of the transport vessels. In contrast, lipedema is a particular syndrome with a poorly understood etiology characterized by fat and water deposits in the subcutaneous tissue (particularly in lower limbs and gluteal muscle), and associated with lymphedema and/or lipodystrophy. Lipedema was described for the first time as an accumulation of subcutaneous fat with hard leg edema excepting the feet. In various descriptions (16), the following observa- tion has always been underlined: foot hypothermia with a localized gradient of tempera- ture. Such pathology, often superficially defined as a lymphedema or venous insufficiency or cellulite, is observed in more than 65% of women between the ages of 14 and 35 years, becoming lipodystrophic lipolymphedema after the age of 40. The common characteristics of a lipolymphedema are the absence of venous insufficiency (eventually secondary) and the close relation with the fat tissue metabolism. Lipolymphedema is a syndrome of unknown etiology, characterized with fat deposi- tion in the subcutaneous tissue and associated with orthostatic and recurrent edema in the legs and gluteal muscle that induces the impression of an increased volume in the limbs. Lipedema always begins in the legs, excluding the ankle and foot, which makes it different from lipolymphedema. It can be related to weight increase but is often independent of it. The characteristic of this extremely frequent disease is that edema always succeeds fat deposition. The latter is subsequent to endocrinometabolic disorder of the interstitial matrix and is not accompanied with obesity. The edema here is not caused by structural changes of veno-lymphatic vessels, but by the modified ratio of the distance from the adiposity and connective structure with a loss of support.

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Just below the vermis is an Should there be an increase in the mass of tissue occupy- opening into a space — the space is the fourth ventricle ing the posterior cranial fossa (e 5 mg finasteride amex. This would and Figure 21) The opening is between the ventricle and force the cerebellar tonsils into the foramen magnum buy finasteride 1mg on line, the subarachnoid space outside the brain (discussed with thereby compressing the medulla purchase finasteride 5 mg on line. The compression, if Figure 21); the name of the opening is the Foramen of severe, may lead to a compromising of function of the Magendie. The complete syndrome is known as tonsillar herni- men is the medulla, its posterior or dorsal aspect. This is a life-threatening situation that significant structure seen here is a small elevation, repre- may cause cardiac or respiratory arrest. Both can be seen in the ventral view of the BRAINSTEM 7 brainstem (see Figure 7). Details of the information car- ried in these pathways will be outlined when the functional aspects of the cerebellum are studied with the motor sys- BRAINSTEM: DORSAL VIEW — CEREBELLUM tems (see Figure 55). The superior cerebellar peduncles REMOVED convey fibers from the cerebellum to the thalamus, passing through the roof of the fourth ventricle and the midbrain This diagram shows the brainstem from the dorsal per- (see Figure 57). This peduncle can only be visualized from spective, with the cerebellum removed. This dorsal perspective is useful (see also Figure 6 and Figure 7). The lower part of the fourth ventricle separates the MIDBRAIN LEVEL medulla from the cerebellum (see Figure 21). The special structures below the fourth ventricle are two large protu- The posterior aspect of the midbrain has the superior and berances on either side of the midline — the gracilis and inferior colliculi, as previously seen, as well as the emerg- cuneatus nuclei, relay nuclei which belong to the ascend- ing fibers of CN IV, the trochlear nerve. The posterior ing somatosensory pathway (discussed with Figure 9B, aspect of the cerebral peduncle is clearly seen. The cranial nerves seen from this view include the PONTINE LEVEL entering nerve CN VIII. More anteriorly, from this oblique Now that the cerebellum has been removed, the dorsal view, are the fibers of the glossopharyngeal (CN IX) and aspect of the pons is seen. The space separating the pons vagus (CN X) nerves, as these emerge from the lateral from the cerebellum is the fourth ventricle — the ventricle aspect of the medulla, behind the inferior olive. The roof of the upper portion of the fourth ventricle is a sheet of nervous tissue and bears the name superior med- ADDITIONAL DETAIL ullary velum; more relevant, it contains an important The acoustic stria (not labeled) shown in the floor of the connection of the cerebellum, the superior cerebellar fourth ventricle are fibers of CN VIII, the auditory portion, peduncles (discussed with Figure 57). The lower half of which take an alternative route to relay in the lower pons, the roof of the fourth ventricle has choroid plexus (see before ascending to the inferior colliculi of the midbrain. Two additional structures are shown in the midbrain As seen from this perspective, the fourth ventricle has — the red nucleus (described with Figure 47 and Figure a “floor”; noteworthy are two large bumps, called the 65A), and the brachium of the inferior colliculus, a con- facial colliculus, where the facial nerve, CN VII, makes necting pathway between the inferior colliculus and the an internal loop (to be discussed with Figure 48 and also medial geniculate body, all part of the auditory system with the pons in Section C of this atlas, see Figure 66C). As the cerebellum has been removed, the cut surfaces The medial and lateral geniculate nuclei belong with of the middle and inferior cerebellar peduncles are seen. The lateral The cerebellar peduncles are the connections between geniculate body (nucleus) is part of the visual system (see the brainstem and the cerebellum, and there are three pairs Figure 41A and Figure 41C). The inferior cerebellar peduncle connects the medulla and the cerebellum, and the prominent middle © 2006 by Taylor & Francis Group, LLC Orientation 35 Red n. Superior colliculus Lateral geniculate Brachium of body inferior colliculus Medial Inferior colliculus geniculate body Cerebral peduncle Trochlear nerve (CN IV) Superior medullary velum Superior cerebellar Trigeminal peduncle nerve (CN V) Middle 4 cerebellar peduncle Facial colliculus Inferior cerebellar peduncle Vestibulocochlear nerve (CN VIII) Glossopharyngeal nerve (CN IX) 4 Vagus nerve (CN X) Cut edge of 4th ventricle Inferior olive Cuneatus n. Cervical spinal cord 4 = Floor of 4th ventricle FIGURE 10: Brainstem 7 — Dorsal View — Cerebellum Removed © 2006 by Taylor & Francis Group, LLC 36 Atlas of Functional Neutoanatomy FIGURE 11 areas of the cortex. In addition, the limbic system has circuits that involve the thalamus. THE DIENCEPHALON: Other thalamic nuclei are related to areas of the cere- bral cortex, which are called association areas, vast areas THALAMUS 1 of the cortex that are not specifically related either to sensory or motor functions. Parts of the thalamus play an THALAMUS: ORIENTATION important role in the maintenance and regulation of the state of consciousness, and also possibly attention, as part The diencephalon, which translates as “between brain,” is of the ascending reticular activating system (ARAS, see the next region of the brain to consider. It will be discussed with the the cerebral hemispheres in the human brain has virtually limbic system in Section D of this atlas (see hidden or “buried” the diencephalon (somewhat like a Figure 78A). This itary stalk and mammillary bodies in Figure 15A and gland is thought to be involved with the regu- Figure 15B, which are part of the hypothalamus).

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