Citations

Purpose Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited. Patients and Methods Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis. Results At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm (P < .001). Similarly, there continues to be a statistically significant 39% reduction in death rate in favor of the trastuzumab-containing arm (P < .001). Conclusion These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date. The clinical benefits continue to outweigh the risks of adverse effects.

Background: Cortical spreading depression (CSD) is a wave of depolarization followed by depression of bioelectrical activity that slowly propagates through the cortex. CSD is believed to be the underlying mechanism of aura in migraine; however, whether CSD can elicit pain associated with migraine headache is unclear. Methods: Awake, freely moving rats were monitored for both CSD events and behavioral responses resulting from dural-cortical pinprick and/or KCl injection to the occipital cortex. Results: We observed tactile allodynia of the face and hindpaws, as well as enhanced Fos expression within the trigeminal nucleus caudalis (TNC) following CSD induced by KCl injection into the cortex, but not by pinprick. Application of KCl onto the dura elicited cutaneous allodynia and increased Fos staining in the TNC but did not elicit CSD events. Conclusions: These data suggest that sustained activation of trigeminal afferents that may be required to establish cutaneous allodynia may not occur following CSD events in normal animals.

Background and Purpose —Intracerebral hemorrhage (ICH) is a highly morbid disease process. Perihematomal edema is reported to contribute to clinical deterioration and death. Recent experimental observations indicate that clotting of the intrahematomal blood is the essential prerequisite for hyperacute perihematomal edema formation rather than blood-brain barrier disruption. Methods —We compared a series of patients with spontaneous ICH (SICH) to a series of patients with thrombolysis-related ICH (TICH). All patients were imaged within 3 hours of clinical onset. We reviewed relevant neuroimaging features, emphasizing and quantifying perihematomal edema. We then analyzed clinical and radiological differences between the 2 ICH types and determined whether these factors were associated with perihematomal edema. Results —TICHs contained visible perihematomal edema less than half as often as SICHs (31% versus 69%, P <0.001) and had both lower absolute edema volumes (0 cc [25th, 75th percentiles: 0, 6] versus 6 cc [0, 13], P <0.0001) and relative edema volumes (0.16 [0.10, 0.33] versus 0.55 [0.40, 0.83], P <0.0001). Compared with SICHs, TICHs were 3 times larger in volume (median [25th, 75th percentiles] volume 69 cc [30, 106] versus 21 cc [8, 45], P <0.0001), 4 times more frequently lobar in location (62% versus 15%, P <0.001), 80 times more frequently contained blood-fluid level(s) (86% versus 1%, P <0.001), and were more frequently multifocal (22% versus 0%, P <0.001). Conclusions —The striking qualitative and quantitative lack of perihematomal edema observed in the thrombolysis-related ICHs compared with the SICHs provides the first substantial, although indirect, human evidence that intrahematomal blood clotting is a plausible pathogenetic factor in hyperacute perihematomal edema formation.

Background and Purpose —The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm 3 . The volume of first-ever ischemic stroke in the population is not known. Methods —The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. Results —There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm 3 (interquartile range, 0.5 to 8.8 cm 3 ). There was a significant relation between location of lesion and infarct size ( P <0.001) and between volume and mechanism of stroke ( P =0.001). Conclusions —The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Abstract In April 2010, a NIH workshop was convened to discuss the current state of understanding of lung cell plasticity, including the responses of epithelial cells to injury, with the objectives of summarizing what is known, what the field needs to know, and how to get there. The proximal stimulus for this workshop is the body of recent evidence suggesting that plasticity is a prominent but incompletely characterized property of lung epithelial cells, and that a focus on understanding this aspect of epithelial cell biology in particular, may be an important window into disease pathobiology and pathogenesis. In addition to their many vital functions in maintaining tissue homeostasis, epithelial cells have emerged as both a central target of disease initiation and an active contributor to disease progression, making a workshop to investigate the role of cell plasticity in lung injury and repair timely. The workshop was organized around four major themes: lung epithelial cell plasticity, signaling control of plasticity, fibroblast plasticity and crosstalk, and translation to human disease. Although this breakdown was recognized to be somewhat artificial, it was felt that this approach would promote cross-fertilization among groups that ordinarily do not communicate and lend itself to the generation of new approaches. The summary reports of individual group discussions below are followed by consensus priorities and recommendations of the workshop participants.

Abstract We studied the status of estrogen (ER) and progesterone (PR) receptors in meningiomas removed from 52 patients, comparing dextran-coated charcoal (DCC), nuclear binding (NB), and immunoperoxidase (IP) assays. Each of the assays was performed independently by investigators well-experienced with these assays. The NB assay is a new assay that measures functional steroid receptors—that is, the activation of the receptor and its binding to the nucleus. The assay is very sensitive and requires a relatively small amount of tissue as compared with the DCC assay. In agreement with data from other studies, PR were detected in most meningiomas by all 3 methods: in 69% of the cases by NB, in 76% by DCC, and in 89% by IP. ER were detected in only a few cases: in 33% by NB, in 2% by DCC, and in none by the IP assay. The agreement for PR sites was 62% for all 3 assays, it was 66% between the NB and DCC assays, 67% between the NB and IP assays, and 86% between the DCC and IP assays. Of 26 cases that were positive by the DCC assay, 6 (23%) were negative by NB. The overall agreement for all three ER assays was 65%. The data suggest that the majority of meningiomas contain high-affinity receptors for progesterone, that estrogen receptors are present in only a few meningiomas, and that some of these estrogen and progesterone receptors appear to be functional.

Abstract Eight surgical and one autopsy specimen of pituitary adenomas (six cases of Cushing's disease, two of Nelson's syndrome. and one of hypopituitarism) were studied by histochemical, immunohistocytological, and ultrastructural methods. Eight tumors showed the characteristic histochemical profile of corticotroph adenoma—amphophilic to basophilic, and periodic acid-Schiff-positive to some extent. In all tumors, immunohistochemical studies revealed adrenocorticotropic hormone (ACTH) and à-subunit in the cytoplasm of some adenoma cells. By electron microscopy, seven tumors were found to be monomorphous; six were typical corticotroph adenomas and one was a subtype II silent corticotroph adenoma. One unique lesion was bimorphous—i.e., composed of corticotrophs as well as cells resembling glycoprotein cells. Immunoelectron microscopy by the double-labeling immunogold technique, performed on one corticotroph adenoma, demonstrated the presence of ACTH and à-subunit not only within the same adenoma cells but also within the same secretory granules. The cytogenesis of ACTH à-subunit tumors, a rare form of plurihormonal adenoma. remains to be elucidated. The duration of disease associated with these tumors exceeded the duration in patients with ordinary corticotroph adenomas. Given the low frequency with which increases in serum à-subunit are detectable in patients with such tumors—13% in this series—hormone production is not recognized at preoperative evaluation.