Citations

Studies in both human and experimental models demonstrate that myelin repair occurs in the central nervous system and is a normal physiologic response to myelin injury. However, remyelination in MS is often incomplete and limited. The outcome of an actively demyelinating lesion depends on the balance between factors promoting myelin destruction and myelin repair. Experimental models of CNS demyelination provide an opportunity to investigate the morphologic, cellular and molecular mechanisms involved in remyelination. This review focuses on experiments using the Theiler's virus model of demylination which indicate that manipulation of the immune response has the potential to promote endogenous CNS remyelination and functional recovery in MS.

The sexually abused child has been described as more fearful, anxious, depressed, and guilty in comparison to normal children. However, these descriptions are largely derived from clinical impressions and little systematic exploration of the nature and extent of behavior problems among these children. The present study investigated the problem behaviors of a group of preschool and elementary-aged sexually abused children (N = 93) in comparison with a sample of nonabused children from a psychiatric outpatient clinic (N = 64) and a sample of nonabused children from a well child clinic (N = 78). Behavioral strengths and weaknesses in these children were examined by administering the Achenbach Child Behavior Checklist to their mothers. Sexually abused children displayed a significantly greater number of behavior problems than normals but were not as significantly disturbed as the psychiatric outpatients. The sexually abused children did display significantly more sexual problems than either comparison group. Caseworkersl therapists for the sexually abused child provided ratings of family conflict, cohesion, and support of the child. These were significantly related to the extent of behavior problems in the sexually abused children. This relationship equaled or exceeded the relationship of severity of sexual abuse to behavior problems.

Purpose The purpose was to compare open and arthroscopic acromioclavicular joint (ACJ) resection. Methods We retrospectively reviewed 103 patients (105 shoulders) who underwent ACJ resection between 2000 and 2005. There were 56 women and 47 men with a mean age of 48 years. The mean duration of follow‐up was 51 months (range, 15 to 91 months). Arthroscopic ACJ resection by use of a direct approach was performed in 81 shoulders (group A), and open ACJ resection was performed in 24 shoulders (group B). Results were graded according to pain relief both subjectively and objectively with cross‐body adduction testing and direct palpation of the ACJ, subjective shoulder value, Constant score, and improved function. Results The Constant scores increased from 50 (range, 34 to 65) to 89 (range, 39 to 100) in group A ( P < .0001) and from 46 (range, 22 to 63) to 87 (range, 43 to 100) in group B ( P < .0001). There was no statistical difference in the postoperative normalized Constant score between group A and group B ( P = .47). Pain with cross‐body adduction testing and palpation of the ACJ improved in 76 shoulders (94%) in group A and 22 shoulders (92%) in group B. No patients had signs or symptoms of ACJ anteroposterior instability. Revision ACJ resection was performed in 5 patients (5 shoulders [6.2%]) in group A and 1 shoulder (4.2%) in group B ( P = .37). The radiographs of the patients who underwent revision showed that 3 patients (3.7%) from group A had regrowth of the distal clavicle; in addition, 2 patients (2.5%) from group A and 1 patient (4.3%) from group B had incomplete distal clavicle excision. Conclusions This study did not show a significant difference in the outcome between arthroscopic and open ACJ resection. Incomplete excision and regrowth of the distal clavicle are the most common causes of revision. Although only the arthroscopic group showed a small percentage of patients (3.7%) with regrowth of the distal clavicle, the number is too small to assume that this complication is the result of the arthroscopic technique only. Level of Evidence Level IV, therapeutic case series.

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Describe the potential therapeutic advantages of tyrosine kinase inhibitors (TKIs) over antibody mediated inhibition with trastuzumab, such as oral bioavailability and ability to cross the blood–brain barrier.Explain the ability of TKIs to overcome resistance to and synergize with trastuzumab.Discuss the multiple tyrosine kinase inhibitors currently in development and their spectrum of targets and toxicities.This article is available for continuing medical education credit at CME.TheOncologist.com.HER-2 is a transmembrane, tyrosine kinase (TK) receptor whose overexpression is associated with adverse prognosis in breast cancer. The biological effects of HER-2 are mediated by kinase activity causing phosphorylation of tyrosine residues in the cytoplasmic domain of the receptor molecule, leading to activation of downstream growth-promoting pathways. Antibody-mediated inhibition by trastuzumab as well as TK inhibition are clinically effective anti–HER-2 strategies. Kinase inhibitors offer some potential therapeutic advantages over antibody-based therapies. Being small molecules, TK inhibitors (TKIs) have oral bioavailability and ability to cross the blood–brain barrier. Because of their different mode of action, TKIs may be able to overcome some of the mechanisms of trastuzumab resistance. Preclinical, and limited clinical data also suggest that TKIs and trastuzumab have synergistic activity. Lapatinib is the only TKI available for clinical use at present, but several molecules with anti–HER-2 activity have been identified and are undergoing evaluation. These differ in the spectrum of kinases that they inhibit, potency of HER-2 inhibition, pharmacokinetic properties, and toxicity profiles, and are at various stages of clinical development. In this article we summarize selected HER-2 TKIs approved for clinical use or in development for which clinical data are available.