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Physiological factors that have only recently begun to be studied include muscle strength purchase cabgolin 0.5 mg line, joint position sense (proprioception) purchase cabgolin 0.5 mg on-line, lower limb balance proven cabgolin 0.5 mg, joint stability and biomechanical alignment. The advantage of a total genome screen for OA genes is that it may elucidate such unknown risk factors. Many researchers expect that genes relating to known structural components of cartilage are the principal candidates to explain the genetic component of OA. However, it may be that unsuspected changes in other tissues (for example bone, capsule, muscle) turn out to be as, if not more, important in the pathogenesis of OA structural change. The better understanding of pain mechanisms in general could also lead to improved treatment of chronic OA pain. We still have incomplete knowledge of the complex processing and modulation of sensory input from pain nerve fibres, particularly with respect to chronic pain perception. The current search for novel analgesic agents that alone or in combination influence pain pathways at different central nervous system sites (peripheral, spinal cord, higher centres) may improve the treatment options for OA as much as for other 72 MANAGEMENT OF OSTEOARTHRITIS chronic pain states. In particular the requirement is for effective but safe agents for moderate to severe pain. It is also likely that methods to widen the applicability and impact of non-pharmacological approaches to chronic pain and “coping” will be forthcoming. Included in this is the more formal harnessing of the placebo response that is such a marked feature in OA clinical trials. Improved application of current knowledge The vast majority of people with large joint OA are managed in primary care by self-management and advice from general practitioners, pharmacists and allied health professionals. Although there are scant data on the quality of care for such people, it appears that many receive suboptimal or even inappropriate treatment and advice, especially with respect to education and lifestyle modification. This is probably also true for those who proceed to secondary care. Improved awareness, knowledge and interest in OA and subsequent wider application of current treatment strategies would make a major impact on the community burden of OA. This contrasts with the common misconception that only novel treatment “breakthroughs” can help someone with OA. If better treatments, or even “breakthroughs”, for OA were to become available, appropriate education of healthcare professionals and efficient delivery of such treatments will still be required. The situation with gout, another chronic locomotor condition, is salutary. We have excellent understanding of the pathogenesis of gout and effective treatments to prevent the formation of the causative urate crystals. It is one of the few rheumatic diseases in which the aim of management is “cure”. Regrettably, however, people correctly diagnosed with gout often persist for years with poorly controlled and undertreated disease. Irrespective of any future advances in OA management, appropriate education of healthcare professionals will always remain a priority. Given its high prevalence and impact, knowledge of large joint OA and its management should always be prominent in the training curriculum of general practitioners and allied health professionals. Developments in surgery Surgical interventions for large joint OA include joint debridement, osteotomies and joint replacements. Cartilage repair as currently practised is an experimental treatment for joint cartilage damage in 73 BONE AND JOINT FUTURES the younger individual, but not for OA. It may significantly delay or prevent the need for a joint replacement. Implant component wear and mechanical loosening are focus areas for research: it is hoped that further improvements in implant materials and design will decrease wear rates and the formation of wear particles. A decrease in wear particles may lessen the risk for implant loosening. Implant fixation may be improved by the introduction of new material surface properties, as well as by the treatment of at risk individuals with drugs such as bisphosphonates or parathyroid hormone.

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Random demyelination may interfere with microtubular transport purchase cabgolin 0.5 mg amex. Diagnosis Electrophysiology with small sensory and motor evoked responses effective 0.5mg cabgolin, denervation on EMG 0.5mg cabgolin free shipping. Prognosis Slow reversal of symptoms with variable degrees of residual numbness and reflex changes, motor symptoms if present. References Casey EB, Jellife EM, Le Quesne PM, et al (1973) Vincristine neuropathy. Brain 96: 69–86 Delattre JY, Vega F, Chen Q (1995) Neurologic complications of immunotherapy. In: Wiley RG (ed) Neurological complications of cancer. Dekker, New York, pp 267–293 Fazeny B, Zifko U, Meryn S, et al (1996) Vinorelbine-induced neurotoxicity in patients with advanced breast cancer pretreated with paclitaxel-a phase II study. Cancer Chemother Pharmacol 39: 150–156 Forman A (1990) Peripheral neuropathy in cancer patients: clinical types, etiology, and presentation, part 2. Oncology Williston Park 4: 85–89 319 Harmers FP, Gispen WH, Neijt JP (1991) Neurotoxic side-effects of cisplatin. Eur J Cancer 27: 372–376 Quasthoff S, Hartung HP (2002) Chemotherapy-induced peripheral neuropathy. J Neurol 249: 9–17 Sahenk Z, Barohn R, New P, et al (1994) Taxol neuropathy; electrodiagnostic and sural nerve biopsy findings. Arch Neurol 51: 726–729 Verstappen CC, Heimans JJ, Hoekman K, et al (2003) Neurotoxic complications of chemo- therapy in patients with cancer: clinical signs and optimal management. Drugs 63: 1549– 1563 Walsh RJ, Clark AW, Parhad IM (1982) Neurotoxic effects of cisplatin therapy. Arch Neurol 39: 719–720 Windebank AJ (1999) Chemotherapeutic neuropathy. Curr Opinion Neurol 12: 565–571 320 Metals Arsenic neuropathy Genetic testing NCV/EMG Laboratory Imaging Biopsy ++ ++ Fig. Meese lines at the nail- bed, in case of arsenic poison- ing and polyneuropathy (cour- tesy Dr. Freymueller, Hermagor, Austria) Anatomy/distribution Massive exposure may demonstrate demyelinating polyradiculoneuropathy, distal axonopathy. Symptoms Painful stocking-glove sensory neuropathy, motor neuropathy usually mild but can be severe. Malaise, nausea, vomiting, mucous membrane irritation. Clinical syndrome/ Hyperkeratosis, darkened skin, Mee’s lines (Fig. Acute signs massive exposure leads to vasomotor collapse and death. Arsenic may inhibit conversion of pyruvate to acetyl CoA. Absent SNAPs and reduced CMAPs, muscle denerva- Diagnosis tion. Arsenic can be detected in hair, nails, and urine in chronic exposure cases. Urine levels greater than 25 mg/24 hrs, unless recent seafood ingestion. BAL or penicillamine, continued for months if neuropathy is refractory. Neuro- Therapy pathy from less fulminant exposure usually stabilizes over a 2 year period. Prognosis related to severity and duration of symptoms. Prognosis Bansal SK, Haldar N, Dhand UK, et al (1991) Phrenic neuropathy in arsenic poisoning. References Chest 100: 878–880 Donofrio PD, Wilbourn AJ, Albers JW, et al (1987) Acute arsenic intoxication presenting as Guillain-Barre-like syndrome. Muscle Nerve 10: 114–120 Oh SJ (1991) Electrophysiological profile in arsenic neuropathy.

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Only after taking the full dose of 4–6 tablets per day thefacts 43 AS-06(37-50) 5/29/02 5:49 PM Page 44 Ankylosing spondylitis: the facts for 4–6 months will you know whether it is going to be of any help purchase cabgolin 0.5mg online. Sulfasalazine may be useful in controlling peri- pheral arthritis of AS generic cabgolin 0.5mg on line, but has no appreciable influence on purely axial (spinal) disease or on peripheral enthesitis cheap cabgolin 0.5 mg line. Because it is frequently effec- tive against inflammatory bowel disease and psoria- sis, it may be especially useful for AS associated with those diseases. However, approximately 20% of patients stop the treatment because of side-effects, which include nausea, stomach upset, abdominal bloating, headaches, skin rashes, and mouth ulcers. On rare occasions sulfasalazine may cause liver problems and abnormal white blood-cell counts due to bone marrow suppression, and that’s why your blood count and liver function must be regularly monitored if you are taking this drug. Methotrexate People with AS with severe peripheral joint involvement which does not respond to NSAIDs or sulfasalazine have sometimes responded to weekly oral methotrexate (Rheumatrex) therapy. Metho- trexate and other immunosuppressants are used in the treatment of chronic inflammatory arthritis, such as rheumatoid arthritis and psoriatic arthritis resistant to conventional therapy. It is also a rela- tively slow-acting anti-rheumatic drug, and anyone taking it should not expect a quick response. Like sulfasalazine, methotrexate is not a pain reliever, but it will help to relieve pain if it can first heal or control the underlying inflammation that con- tributes to the pain. It is usually well tolerated but can cause loss of appetite, nausea, diarrhea, hair loss, cough, and 44 thefacts AS-06(37-50) 5/29/02 5:49 PM Page 45 Drug therapy bruising. You should tell your doctor right away if you get a dry cough, fever, or difficulty in breathing. Liver and blood tests and a chest X-ray are advised before starting the drug, and the treatment is moni- tored for side-effects by liver tests and blood counts. Methotrexate is not suitable for people with liver and lung disease, alcoholism, an abnormal blood count, or active infection. Methotrexate may temporarily reduce fertility in men and women, but the risk appears to be very low, as far as we can tell at present. Therefore, it is sensible to wait for 6 months after discontinuing the drug before attempting to start a baby. This allows for drug washout and avoids any theoretical risk of fetal exposure. Methotrexate may cause birth defects if taken during pregnancy. The most vulnerable period is between 6 and 8 weeks of pregnancy at a critical methotrexate dose of more than 10 mg weekly. Breastfeeding should also be avoided while a woman is taking methotrexate. Corticosteroids Oral corticosteroids are powerful anti-inflammatory drugs but cause a number of side-effects, including osteoporosis (discussed in Chapter 9), weight gain, thinning of the skin, cataract in the eye, elevation of blood pressure, raised blood sugar, poor wound healing, and increased susceptibility to infections. They have no therapeutic value in the long-term management of the musculoskeletal aspects of AS because of their serious side-effects, and they do not stop the progression of the disease. Local corti- costeroid injection, however, is quite helpful in thefacts 45 AS-06(37-50) 5/29/02 5:49 PM Page 46 Ankylosing spondylitis: the facts controlling persistent joint inflammation and enthesitis. The benefit of injection into the sacroil- iac joints is currently being evaluated. New drug treatments TNF-based therapy Results of clinical trials now provide encouraging evidence of a prompt and dramatic improvement in symptoms for patients with a variety of ailments when treated with drugs that block the action of a natural substance in the body called tumor necrosis factor alpha (TNF, for short). The diseases that can be treated include severe forms of rheumatoid arthritis, juvenile idiopathic arthritis (also called juvenile rheumatoid arthritis), and many other inflammatory diseases, including Crohn’s disease, that are resistant to conventional therapy. Anti-TNF therapy has now been found to be very effective in severe AS, psoriatic arthritis, and other spondyloarthropathies that are unresponsive to con- ventional therapy. However, it can have serious side-effects, and whether it is safe as a long-term therapy also remains to be seen. TNF is a cytokine produced by certain inflamma- tory cells.

The most important risk factor in the development of these lesions is family history Key Concept/Objective: To know that actinic keratosis is a potential precursor to squamous cell carcinoma of the skin This patient has hyperkeratotic lesions typical of actinic keratosis in sun-exposed areas order cabgolin 0.5 mg line. Actinic keratosis is seen in areas of chronically sun-damaged skin and is considered a pre- cursor lesion to the development of SCC purchase 0.5 mg cabgolin visa. The majority of patients with actinic keratosis have multiple lesions cabgolin 0.5mg discount, and the risk of SCC in these patients is estimated to be as high as 20%. Thus, it is important that the patient be followed regularly and evaluated by a der- matologist: the removal of these lesions through various techniques can prevent progres- sion to cancer. Small SCCs that arise from actinic keratosis lesions are actually less likely to metastasize than more atypical SCCs, such as those that are poorly differentiated or appear in non–sun-exposed areas or oral or genital mucosa. Sunlight exposure is the most important risk factor for developing actinic keratosis and SCC, although radiation, chem- ical burns, and chronic nonhealing wounds may also predispose to squamous cell cancer. A 59-year-old white woman with rheumatoid arthritis who was treated in the past with methotrexate and courses of steroids presents for evaluation of a mole on her chest. She states that it has been present for years but that, in the past 6 to 8 months, she noticed more irregularity at the borders and an increase in the size of the lesion. Examination reveals an asymmetrical lesion approximately 8 mm in diameter that is variably pigmented from brown to black. You recommend biopsy of the lesion because you are concerned about malignant melanoma. If a primary cutaneous melanoma is confirmed, which of the following factors would be the most important with regard to outcome in this patient? Evolution of the lesion from a dysplastic nevus B. Location of the melanoma Key Concept/Objective: To understand the importance of tumor thickness as a prognostic factor in primary cutaneous melanoma Malignant melanoma is the most aggressive of the primary cutaneous malignancies, and the clinician should have a high index of suspicion when evaluating moles with the char- acteristics of melanoma. The “ABCD” mnemonic is useful for remembering the features of melanoma: asymmetry, border irregularity, color variation, and diameter greater than 6 mm. In this patient, the change in the size of a mole over time also warrants prompt evaluation. The single strongest prognostic factor in melanoma is stage of disease at the time of diagnosis. Staging takes into account tumor size, nodal involvement, and distant metastases. For primary tumors, the most consistent factor predictive of outcome is tumor thickness, as described by the Breslow depth. A 35-year-old white man presents at a walk-in clinic with a complaint of lesions in his mouth and over his trunk. These lesions developed over the past several months. He states that he is homosexual, that he has practiced unsafe sex in the past, and that he has had the same partner for the past 18 months. He denies having previously had any sexually transmitted diseases, but he says he has not had regular health care visits since high school. On examination, you note numer- ous purple-red, oval papules distributed on the trunk and two deep-purple plaques on the soft palate and buccal mucosa. The patient also has several small, firm, nontender, palpable lymph nodes in the poste- rior cervical, axillary, and inguinal chains. Results of routine blood work are unremarkable except for a white blood cell count of 3,000 cells/mm3 and a differential with 5% lymphocytes. Which of the following statements regarding our current knowledge of Kaposi sarcoma (KS) is false? Human herpesvirus 8 (HHV-8) plays an etiologic role exclusively in HIV-associated KS B. If HIV infection is confirmed, initiation of highly active antiretroviral therapy (HAART) in this patient would likely lead to dramatic improvements in the lesions during the first few months of therapy D. Male sex is a significant risk factor for the condition, especially in the classic form of the disease E. Total CD4+ T cell count is the most important factor predictive of sur- vival in the form of this disease associated with HIV Key Concept/Objective: To be able to recognize KS and appreciate important aspects of its diag- nosis and treatment This patient is a homosexual man who presents with skin and oral lesions typical of KS. The additional findings of generalized lymphadenopathy and lymphopenia strongly sug- gest that the patient is infected with HIV.

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