Characterization of Biopharmaceuticals Focusing on Antibody Therapeutics

Biopharmaceuticals are highly complex molecules and also require high quality for safety and efficacy in human uses. For well-characterized products, the desired level of quality should be monitored and controlled during the manufacturing processes. A series of workflow for analytical characterization should be applied for product quality throughout those processes. In this chapter, several analytical techniques are introduced for assessing characteristics of biopharmaceuticals focusing on monoclonal antibodies (mAbs). Analytical characterization for primary structure was performed by mass spectrometry (MS), and assessment of post-translational modifications (PTMs) was done by conventional approaches. The analytical assessments were also done by multi-attribute method (MAM) approach using mass spectrometer (MS), and the performance of MAM was compared to conventional approaches

Clinical Manifestations of Recurrent Parotid Pleomorphic Adenoma

Objectives. This study was undertaken to confirm the clinical characteristics of recurrent pleomorphic adenoma (RPA), and to identify those factors that affect the development of malignant transformation (MT) from RPA. Methods. The medical records of 270 patients, who were operated upon for parotid PA, were retrospectively reviewed. The pathologic specimens of a selected series of 23 patients were reviewed for histologic subtype and microscopic multi-nodularity. Results. Mean age of initial operation in RPA without MT (RPA(-MT)) group was significantly lower than that of primary PA group. Mean age of the revision operation in RPA with MT (RPA(+MT)) group was significantly greater than that of RPA(-MT) group. Mean interval from operation to recurrence shortened after each revision operation. The risk of MT and additional recurrence increased significantly with recurrence. In RPA(-MT) group tumor recurrence occurred in 21.4% of patients despite a clear resection margin. Conclusion. The risk factors for MT may be an age of over 45 yr and multiple recurrences. However, younger patients are more at risk of recurrence. A clear resection margin cannot guarantee a cure in RPA, and it seems that parotid pleomorphic adenomas slowly gain malignant characteristics after repeated recurrences.SUH MW, 2005, KOREAN J HEAD NECK O, V21, P146HANNA EY, 2005, CUMMINGS OTOLARYNGOL, P1348Ghosh S, 2003, CLIN OTOLARYNGOL, V28, P262Glas AS, 2002, CANCER, V94, P2211, DOI 10.1002/cncr.10445Glas AS, 2001, HEAD NECK-J SCI SPEC, V23, P311BRADLEY PJ, 2001, CURR OPIN OTOLARYNGO, V9, P100Carew JF, 1999, OTOLARYNG HEAD NECK, V121, P539Junquera L, 1999, HEAD NECK-J SCI SPEC, V21, P652Hancock BD, 1999, ANN ROY COLL SURG, V81, P299Bankamp DG, 1999, LARYNGO RHINO OTOL, V78, P77Hoorweg JJ, 1998, EUR J SURG ONCOL, V24, P452Henriksson G, 1998, CANCER, V82, P617Laskawi R, 1998, BRIT J ORAL MAX SURG, V36, P48Klijanienko J, 1997, HEAD NECK-J SCI SPEC, V19, P629Leverstein H, 1997, EUR ARCH OTO-RHINO-L, V254, P313SunardhiWidyaputra S, 1995, PATHOL RES PRACT, V191, P1186PHILLIPS PP, 1995, ANN OTO RHINOL LARYN, V104, P100BUCHMAN C, 1994, LARYNGOSCOPE, V104, P1231NATVIG K, 1994, HEAD NECK-J SCI SPEC, V16, P213JACKSON SR, 1993, J LARYNGOL OTOL, V107, P546MCGREGOR AD, 1988, BRIT J PLAST SURG, V41, P177FEE WE, 1978, LARYNGOSCOPE, V88, P265SEIFERT G, 1976, HNO, V24, P415NAEIM F, 1976, ARCH PATHOL LAB MED, V100, P271FRAZELL EL, 1954, CANCER, V7, P637

Traumatic Cervical Cord Transection without Facet Dislocations-A Proposal of Combined Hyperflexion-Hyperextension Mechanism: A Case Report

A patient is presented with a cervical spinal cord transection which occurred after a motor vehicle accident in which the air bag deployed and the seat belt was not in use. The patient had complete quadriplegia below the C5 level and his imaging study showed cervical cord transection at the level of the C5/6 disc space with C5, C6 vertebral bodies and laminar fractures. He underwent a C5 laminectomy and a C4-7 posterior fusion with lateral mass screw fixation. Previous reports have described central cord syndromes occurring in hyperextension injuries, but in adults, acute spinal cord transections have only developed after fracture-dislocations of the spine. A case involving a post-traumatic spinal cord transection without any evidence of radiologic facet dislocations is reported. Also, we propose a combined hyperflexion-hyperextension mechanism to explain this type of injury

Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

CONTEXT: Industrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers. CASE PRESENTATION: Five workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis. DISCUSSION: Infectious hepatitis and drug-induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction–type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: In the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers’ health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent