Low-frequency stimulation reverses kindling-induced neocortical motor map expansion.

Repeated application of low-frequency stimulation can interrupt the development and progression of seizures. Low-frequency stimulation applied to the corpus callosum can also induce long-term depression in the neocortex of awake freely moving rats as well as reduce the size of neocortical movement representations (motor maps). We have previously shown that seizures induced through electrical stimulation of the corpus callosum, amygdala or hippocampus can expand the topographical expression of neocortical motor maps. The purpose of the present study was to determine if low-frequency stimulation administered to the corpus callosum could reverse the expansion of neocortical motor maps induced by seizures propagating from the hippocampus. Adult Long-Evans hooded rats were electrically stimulated in the right ventral hippocampus, twice daily until 30 neocortical seizures were recorded. Subsequently, low-frequency stimulation was administered to the corpus callosum once daily for 20 sessions. High-resolution intracortical microstimulation was then utilized to derive forelimb-movement representations in the left (un-implanted) sensorimotor neocortex. Our results show that hippocampal seizures result in expanded motor maps and that subsequent low-frequency application can reduce the size of the expanded motor maps. Low-frequency stimulation may be an effective treatment for reversing seizure-induced reorganization of brain function.

Diagnostic value of hepatocyte paraffin 1 antibody to discriminate hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration biopsies of the liver.

BACKGROUND: Diagnosing liver tumors by fine-needle aspiration biopsy is safe and accurate. However, there are cases that prove diagnostically difficult. Traditionally, immunostains for alpha-fetoprotein and polyclonal carcinoembryonic antigen have been used to distinguish adenocarcinomas from hepatocellular carcinomas (HCCs). In poorly differentiated tumors, these immunostains have limitations in both sensitivity and specificity. An hepatocyte-specific immunostain has been described in the surgical pathology literature. To the authors' knowledge, this hepatocyte antibody has not been studied in liver fine-needle aspiration biopsies. The authors examined the Hepatocyte Paraffin 1 (HP1) antibody for its diagnostic utility in this cytologic setting. METHODS: Cell-block material from 40 cases of HCC and 53 cases of metastatic adenocarcinoma were studied. Slides were stained for HP1 by the avidin-biotin complex method following antigen retrieval. The percentage of malignant cells that exhibited coarse granular staining in the cytoplasm was estimated for all cases of HCC, poorly differentiated HCC, and metastatic adenocarcinoma. RESULTS: HP1 was expressed in 83% of all HCCs but in only 56% of poorly differentiated HCCs. Only 2 of 53 (4%) of metastatic tumors expressed HP1. The overall sensitivity of HP1 was 79% and its specificity was 96%. CONCLUSION: HP1 was found to be a specific immunostain that may prove helpful in diagnosing all but the most undifferentiated liver tumors biopsied by fine-needle aspiration.

Differentiating large cell lymphoma from indolent small B-cell lymphoma in fine needle aspirates using p53, PCNA and transformed lymphocyte count.

OBJECTIVE: To determine the usefulness of proliferating cell nuclear antigen (PCNA), p53 protein expression and transformed lymphocyte count (TLC) as adjunctive tests to differentiate indolent small B-cell lymphoma from large cell lymphoma in fine needle aspiration biopsies. STUDY DESIGN: Aspirates of lymphoproliferative disorders from April 1993 to January 1997 were reviewed. The percentage of TLCs was determined on the Papanicolaou smear. The percentage and intensity of p53 and PCNA immunocytochemical staining was evaluated on cell block sections. These results were compared and correlated with the final diagnoses based on available morphology, flow cytometry and clinical history. RESULTS: There were 40 cases of non-Hodgkin's lymphoma and 12 reactive lymph nodes. Adequate cell blocks were available on 16 large cell lymphomas, 7 grade 1-2 follicular center cell lymphomas, 6 mucosal associated lymphoid tissue lymphomas, 2 small lymphocytic lymphomas and 2 mantle cell lymphomas. Average TLC and p53 nuclear staining was highest in large cell lymphomas (57% TLC and 24% p53), followed by grades 1 and 2 follicular lymphomas (14% TLC and 15% p53) and lowest in other indolent lymphomas (< 10% TLC and < 1% p53). Average PCNA staining was highest in large cell lymphomas (46%) and lowest in small lymphocytic lymphomas (7%); however, TLC was the best parameter for differentiating large cell lymphoma from indolent small B-cell lymphoma. CONCLUSION: TLC differentiated large cell lymphoma from indolent small B-cell lymphoma better than either p53 or PCNA alone or in combination. Significant overlap between categories limits usefulness of these immunocytochemical stains for differentiating these entities.

Diagnosis of lymphoma by fine-needle aspiration cytology using the revised European-American classification of lymphoid neoplasms.

BACKGROUND: Recent changes in the classification of non-Hodgkin lymphoma (NHL) emphasize the diagnostic importance of cytomorphology, immunophenotyping, and molecular findings in addition to histology. These changes have allowed for a greater role of fine-needle aspiration cytology (FNA) in the diagnosis of NHL. METHODS: A review of the English language literature regarding the use of FNA in the cytodiagnosis of lymphoma was performed. The revised European-American classification of lymphoid neoplasms (REAL) was reviewed in the context of its adaptability to the cytologic diagnosis of lymphoid neoplasms. RESULTS: FNA is being used more frequently in the diagnosis, staging, and follow-up of lymphoma whenever supportive studies are readily available. Cytomorphologic, immunophenotypic, and molecular criteria as well as pitfalls in the diagnosis of lymphoma by FNA have been delineated. Information was compiled into tables to facilitate correlation of criteria with the proposed REAL system. CONCLUSIONS: Many cases of NHL can be diagnosed and subclassified by FNA when there is adequate immunophenotypic information. Cancer (Cancer Cytopathol)

Utilization of fine-needle aspiration cytology and flow cytometry in the diagnosis and subclassification of primary and recurrent lymphoma.

BACKGROUND: The primary diagnosis of non-Hodgkin's lymphoma/leukemia (NHL) by fine-needle aspiration (FNA) is controversial. The authors reviewed their experience with FNA and flow cytometry (FC) to determine the usefulness and limitations of these techniques in the diagnosis of NHL. METHODS: Slides and reports from all lymph node and extranodal FNAs performed during the period July 1993 to January 1997 with a diagnosis of lymphoma or benign lymphoid process were reviewed. Clinical and biopsy follow-up data were recorded. Results were tabulated and the usefulness of cytology was analyzed. RESULTS: There were 100 adequate aspirates from 87 patients. These included 72 cases of NHL, 58 (80%) of which were diagnosed by FNA and FC without the need for histologic sampling (69% of the primary lymphomas and 88% of the recurrent lymphomas). There were 22 aspirates suspicious for lymphoma, 12 equivocal results, and 7 benign diagnoses. Eighty-six percent of malignant FNAs (50 of 58) had flow cytometry (FC) as compared with only 15% (5 of 34) of the suspicious or equivocal FNAs. CONCLUSIONS: FNA is a valuable method for diagnosing and subclassifying NHL, although immunophenotyping by FC is often an essential ancillary test. In our experience, correlating the FNA results with the FC results can eliminate the need for a more invasive surgical biopsy in many cases.

Preoperative chemotherapy of chemoradiotherapy for the treatment of adenocarcinoma of the pancreas and ampulla of Vater.

Much has been written about preoperative strategies in the treatment of pancreatic adenocarcinoma, yet there has been very little comment concerning other periampullary malignancies. This review discusses current issues relevant to the further development of preoperative adjuvant treatment of pancreatic adenocarcinoma. A small series of patients with ampullary adenocarcinomas treated with preoperative adjuvant chemoradiotherapy is also described.

The value of transformed lymphocyte count in subclassification of non-Hodgkin's lymphoma by fine-needle aspiration.

No established criteria exist for predicting lymphoma grade or transformation in cytologic material. We counted transformed lymphocytes in fine-needle aspiration (FNA) biopsy specimens to determine whether the percentage of these cells in the smear could predict the histologic grade, the biologic behavior, or both. The percentage of transformed lymphocytes out of total lymphoid cells was determined on Papanicolaou-stained smears. Afterward, a cytodiagnosis was based on clinical information available at the time of the FNA, cytomorphologic data, and flow cytometry data. Results were correlated with results of examination of the surgical biopsy specimen, clinical behavior of the lymphoma, or both. The percentage of transformed lymphocytes was 10% or less in all low-grade or indolent lymphomas. Aspirates with transformed lymphocyte counts of 20% or greater were aggressive lymphomas. We also report our experience in the diagnosis of non-Hodgkin's lymphoma by FNA using cytomorphologic examination and immunophenotyping by flow cytometry at a cancer referral hospital. This is a preliminary study, and larger series may help establish the ranges of transformed lymphocyte counts that correlate with the lymphoma subtype.

Zinc co-ordination in the DNA-binding domain of the yeast transcriptional activator PPR1.

The structure of the native zinc form of the DNA binding domain in the yeast transcriptional activator PPR1 was investigated by extended X-ray absorption fine structure (EXAFS). By carrying out the EXAFS measurements at 11k we were able to demonstrate explicitly the proximity of the two zinc ions (Zn-Zn distance = 3.16 +/- 0.03 A) and the presence of bridging cysteine ligands. The results show that the six cysteine residues co-ordinate two zinc ions in a two-metal ion cluster. PPR1 is the first member of this class of protein for which such information has been obtained.

Interobserver variability of cervical smears with squamous-cell abnormalities: a Philadelphia study.

The reproducibility of reporting squamous lesions by the Bethesda System (TBS) was evaluated by distributing 20 slides to be classified among 5 panelists considered experts in the field of cytopathology. Four cases were chosen for their classic morphology and the remainder were foreseen to produce possible discrepancies within one diagnostic category. For 7/20 (35%) cases there was unanimous agreement. Participants disagreed within one category of magnitude for seven (35%) cases. In six (30%) cases there was a range of more than one category disagreement. However, additional written comments modifying TBS diagnoses often diminished the clinical significance of these discrepancies. We conclude that despite the important role of TBS in standardization of Pap smear reports, a great degree of subjectivity exists in classifying squamous abnormalities without "classic" morphology. The lack of reproducibility should be taken into account in cytology proficiency testing.

Three-dimensional volumetric ultrasound imaging of arterial pathology from two-dimensional intravascular ultrasound: an in vitro study.

The objectives of this study were to evaluate: (1) the feasibility of generating three-dimensional (3-D) ultrasound (US) volumetric images of arterial segments from intravascular (IV) US images by retaining full range of gray levels; (2) the feasibility of volumetric quantitation of various arterial wall pathology from the 3-D volume US images of arterial segments. IVUS provides morphologic details of arterial wall diseases. This is seen as variation in gray levels. However, when a 3-D US image is generated currently, the full range of gray levels is not utilized. This limits optimal assessment of arterial wall pathology. Sequential cross-sectional IVUS images from 11 arterial segments consisting of various pathology were obtained in vitro by calibrated withdrawal of an IVUS catheter. These images were digitized by an 8 bit digitizer to retain full 256 gray levels of brightness. 3-D volume generation was carried out using "ANALYZE" software. After the IVUS imaging, arterial segments were sectioned transversely in a 0.3-0.4 mm cross section and stained with hematoxylin, eosin and elastin. Geometrical measurements and gross morphological changes of the arterial segments were noted and correlated with the corresponding section of the image from the three-dimensional volume. Arterial wall pathology, its extent and its effect on lumen geometry were easily appreciated in multiple tomographic sections of a 3-D volume image. Similarly, arterial wall pathology was easily quantitated from 3-D volume. The above assessments were only feasible by retaining full range of gray levels in the 3-D volume image. This study indicates that (1) it is feasible to generate a 3-D US volume image by retaining full range of gray levels from IVUS images, (2) retaining full range of gray levels allows optimal assessment of arterial wall pathology and its extent in 3-D volume, and (3) IVUS allows quantitation of arterial wall pathology, and thereby one can assess the effect of intervention.

Ischemic changes in fetal myocardium. An autopsy series.

It has been assumed that fetal myocardial necrosis is an uncommon event that occurs only under unusual circumstances. We studied random heart sections on 76 fetal and perinatal autopsies from a 4-year period to determine the types and frequency of histologic abnormalities that occur in fetal myocardium. Vacuolar degeneration was extremely common (43% of stillbirths, 84% of live births) but a nonspecific finding. Ischemic changes, which are typically associated with coagulation necrosis, myofiber waviness, or contraction band necrosis, were seen in 21% of stillbirths and 32% of live births. In the majority of cases with histologic evidence of ischemic change, a combination of either contraction band necrosis, coagulation necrosis, and/or myofiber waviness was identified. Only rarely was any one of the abnormalities seen as an isolated feature. In only two autopsies were the ischemic changes identified in the initial autopsy report. We conclude that the histologic changes associated with ischemia that may represent myocardial necrosis are not uncommon and are frequently overlooked at autopsy.