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Bortezomib, a selective, reversible inhibitor of the proteasome, was recently approved for treatment of multiple myeloma157 Treatment-emergent neuropathy or symptomatic worsening of the neuropathy developed in 35% (90/256) of myeloma patients in treatment trials: 37% (84/228) of patients receiving bortezomib 13 mg/m2 and 21% (6/28) receiving 10 mg/m2 160,161 Polyneuropathy also occurred in 9/21 patients with renal cell carcinoma treated with bortezomib162 The risk of neuropathy correlates with the cumulative dose of bortezomib After reaching a cumulative dose of approximately 30 mg/m2 , the estimated probability of experiencing peripheral neuropathy was 50% in the overall population and 37% in the subset of patients without peripheral neuropathy at baseline160,161 Patients usually complain of paresthesia, burning dysesthesia, and numbness in a length-dependent distribution The neuropathy usually improves when the dose is reduced or drug is discontinued The electrophysiological characteristics of the treatment-emergent neuropathy suggest a length-dependent, axonal, sensory polyneuropathy161,163 The absence of electrophysiological changes in some patients with symptoms of burning and dysesthesias in their feet suggests involvement of small-diameter nerve bers (ie, a small ber neuropathy) as well Recent studies and our own research suggest that bortezomib may block the ubiquitin proteasome pathway, possibly causing a build-up of proteins that should be degraded by the proteasome, resulting in impairment of neuronal function, initially in the dorsal root ganglia, and then leading to retrograde (or dying-back ) axonopathy of small nerve bers followed by larger nerve bers

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var my_ary:Array = new Array();

Neuropathy is not an uncommon complication in a cancer patient with cancer Although a paraneoplastic etiology is often considered, most neuropathies in the setting of cancer are not the result of an immune-mediated remote effect of cancer The neuropathy may be due to adverse side effects of chemotherapeutic agents (toxic neuropathy), nutritional, or due to compression or in ltration of the tumor Treatment and prognosis are dependent on the etiology of the neuropathy

sum = 0; for ( i=0; i<100; i++ ) sum += myNumber[ i ]; printf( "The sum of the 100 numbers is %d.", sum );

1 Briemberg HR, Amato AA Neuromuscular complications of cancer Neurol Clin 2003;21(1):141 165

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As discussed earlier, arrays hold multiple data values The values of an array are stored in numerical order Items in an array can be referenced by their numerical position, which in an array is called an index number The first index of an array is always zero, and array indices are always referenced using square brackets ([])

In the preceding example, the for loop is used to step through an array, performing some operation on each of the array s elements. You ll use this technique frequently in your own C programs.

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sensory neuronopathy: A morphologic study Neurology 1197;49:1156 1159 Lennon VA, Sas DF, Busk MF, et al Enteric neuronal autoantibodies in pseudo-obstruction with small-cell lung carcinoma Gastroenterology 1991;100:137 142 Altermatt HJ, Rodriguez M, Scheithauer BW, Lennon VA Paraneoplastic anti-Purkinje and type-1 anti-neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells Lab Invest 1991;65:412 420 Jean WC, Dalmau J, Ho A, Posner JB Analysis of the IgG subclass distribution and in ammatory in ltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis Neurology 1994;44:140 147 Rosenblum MK Paraneoplastic and autoimmunologic injury of the nervous system: The anti-Hu syndrome Brain Pathol 1993:3:199 212 Voltz RD, Graus F, Posner JB, Dalmau J Paraneoplastic encephalomyelitis: An update on the effects of the anti-Hu immune response J Neurol Neurosurg Psychiatry 1997;63:133 136 Sillevis-Smith PAE, Manley GT, Posner JB Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause disease in mice Neurology 1995;45:1873 1878 Panegyres PK, Reading MC, Esiri MM The in ammatory reaction of paraneoplastic ganglionitis and encephalitis: An immunohistochemical study J Neurol 1993;240:93 97 Benyahia B, Liblau R, Merle-B ral H, Tourani J-M, Dalmau e J, Delattre J-Y Cell-mediated autoimmunity in paraneoplastic neurological syndromes with anti-Hu antibodies Ann Neurol 1999;45:162 167 Voltz R, Dalmau J, Posner JB, Rosenfeld MR T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis Neurology 1998;51:1146 1150 Bastson OA, Fantle DM, Stewart JA Paraneoplastic encephalomyelitis Dramatic response to chemotherapy alone Cancer 1992;69:1291 1293 Keime-Guibert F, Graus F, Bro t P, et al Clinical outcome of e patients with the anti-Hu-associated encephalomyelitis after treatment of the cancer Neurology 1999;53:1719 1723 Graus F, Vega F, Delattre JY, et al Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes and antineuronal antibodies Neurology 1992;42:536 540 Antoine JC, Mosneir JF, Honnorat J, et al Paraneoplastic demyelinating neuropathy, subacute sensory neuropathy, and anti-Hu antibodies: Clinicopathological study of an Autopsy case Muscle Nerve 1998;21:850 857 Graus F, Keime-Guibert F, Rene R, et al Anti-Huassociated paraneoplastic encephalomyelitis: Analysis of 200 patients Brain 2001;124:1138 1148 Amato AA, Anderson MP A 51 year old woman with lung cancer and neuropsychiatric abnormalities (Case 38 2001) N Engl J Med 2001;354:1758 1765 Amato AA, Barohn RJ, Sahenk Z, Tushka PJ, Mendell JR Polyneuropathy complicating bone marrow and solid organ transplantation Neurology 1993;43:1513 1518 Gabriel SE, Conn DL, Phyliky RL, Pittelkow MR, Scott RE Vasculitis in hairy cell leukemia: Review of literature and consideration of possible pathogenic mechanisms J Rheumatol 1986;13:1167 1172.

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