Search

Background: Catenin/E-cadherin complex proteins play an important role in cell-cell adhesion with decreased expression correlating with adverse prognostic variables in several human malignancies., Methods: Archival formalin fixed, paraffin embedded (FFPE) sections from 118 prostatic adenocarcinomas (PACs) were immunostained by an automated method (Ventana Medical Systems, Tuscon, AZ) using monoclonal antibodies to catenins alpha and beta, p120 CTN, and E-cadherin proteins. Immunoreactivity was semiquantitatively graded, and results correlated with traditional prognostic parameters. In a subset of 10 randomly selected cases, E-cadherin gene promoter methylation status was determined on FFPE tissues using sodium bisulfite/hydroquinone DNA modification and polymerase chain reaction (PCR) with methylation specific primers (CpG wiz E-cadherin methylation assay; Intergen Co., Purchase, NY)., Results: Decreased expression of alpha-catenin (17%), beta catenin (4%), p120 CTN (45%), and E-cadherin (25%) proteins was noted in PACs with downregulation of each protein correlating with high tumor grade (P = 0.01-0.0001). In addition, p120 CTN and E-cadherin expression levels correlated with pathologic stage (P = 0.05; P = 0.02), aneuploidy (P = 0.001; P = 0.0001), and alpha-catenin with aneuploidy (P = 0.0001). p120 CTN loss also correlated with preoperative serum prostate specific antigen (P = 0.05). Two of 10 cases featured no evidence of E-cadherin gene promoter methylation by PCR and both cases retained expression of E-cadherin protein on immunohistochemistry. Of the 8 cases that showed E-cadherin methylation, 5 (68%) featured loss of expression of the protein on immunohistochemistry (P = 0.11). There was no correlation between E-cadherin methylation and adverse prognostic variables., Conclusions: Decreased expression of catenin/E-cadherin complex cell adhesion proteins is associated with aggressive phenotype in prostatic adenocarcinoma. E-cadherin gene promote methylation is a common event in prostate carcinoma but does not appear to bear prognostic significance in the subset of cases analyzed., (Copyright 2001 American Cancer Society.)

7 patients allergic to cocamidopropyl betaine (CAPB) were detected by positive patch test reactions to Tegobetaine L7TM. These patients were then asked to participate in further testing to its potential impurities, cocamidopropylamine and 3-dimethylaminopropylamine (DMAPA). 4 of the 7 patients were tested to purified CAPB and cocamidopropylamine, with 2 reacting to the purified betaine on allergy patch testing and 3 reacting to cocamidopropylamine 0.1%. At another date, 6 of the 7 were successfully recalled for testing to DMAPA in the presence of sodium lauryl sulfate (SLS) or pure CAPB; 1/6 reacted to DMAPA in water, but only at very high concentrations, at least 3 orders of magnitude higher than that to which skin exposure would occur from use of products containing CAPB. Both SLS and CAPB increased the number of reactions recorded to high levels of DMAPA. However, positive reactions to much lower concentrations of DMAPA (>or=100 ppm) were found in only 1/6 subjects and then only in the presence of the irritant SLS. 0/6 reacted to pure CAPB alone. Taken together, these results suggest that DMAPA is unlikely to be an important contact allergen in CAPB of appropriate quality. They also confirm that CAPB of suitable purity, where levels of both cocamidopropylamine and DMAPA are minimized, is unlikely to trigger reactions in those ostensibly allergic to the material.

Malignant melanoma (MM) is considered to be a chemotherapy-refractory tumor. New anti-cancer drugs (e.g. etoposide) that target DNA topoisomerases (e.g. topoisomerase II-alpha (topo IIalpha)) show activity against a wide variety of solid tumors. In this study, we investigated the frequency and rate of labeling for topo IIalpha in 163 MMs (primary and metastatic) and 67 melanocytic nevi to determine whether topo IIalpha expression is elevated in MM. Primary MM exhibited significantly more frequent topo IIalpha expression compared to benign nevi (86% vs. 56%, p=0.0001). The rate of topo IIalpha labeling in dysplastic melanocytic nevi, radial growth phase MM, vertical growth phase MM and metastatic MM revealed significant differences amongst groups and a positive covariance with advancing stage (means: 0.3, 0.5, 5, and 8 '+' cells/hpf, respectively; r=0.3, all p < or = 0.02). Topo IIalpha labeling significantly correlated with increasing mitotic activity, depth of invasion and Clark's level, diminishing tumor infiltrating lymphocytes, and poor outcome (all p < or = 0.01) in primary MM. For metastatic MM, a minority (30%) exhibited marked elevation of topo IIalpha expression. These findings indicate topo IIalpha as a potential therapeutic target and marker for MM. Immunohistochemical analysis of disseminated MM may allow for correlation with clinical response and enable selection of candidates sensitive for specific chemotherapy.

Disruption of the cell-cycle regulation through over-expression or mutation of cyclins and cyclin-dependent kinases has been implicated in carcinogenesis. In order to determine whether keratoacanthoma (KA) is unique or a variant of squamous cell carcinoma (SCC) and whether expression of mitosis-related antigens are associated with KAs' tendency to regress, we compared the immunohistochemical expression of mitotic cyclins (cyclins A and B) and their cyclin-dependent kinase p34(cdc2) in 21 KAs, 8 regressing KAs, and 28 conventional squamous cell carcinomas. KAs showed both overlap and significant differences in expression of these mitosis-related antigens compared to SCCs. Basal and parabasal pattern of expression of cyclins A and B significantly predominated in KAs in contrast to SCCs which exhibited diffuse pattern (cyclin A 86%/cyclin B 64% vs. 25%/36%, p < 0.01). However, no differences in the highest mean level of expression in 'hot spot' loci of cyclins A and B were identified comparing KAs to SCCs (19%/12% vs. 25%/13%, p > 0.05). For the cyclin-dependent kinase p34(cdc2), no differences in pattern, distribution or mean levels of expression were found. For cyclins A and B, regressing KA showed significantly more regional tumor labeling (88%/88% vs. 57%/33%, p = 0.03) and a lower mean level of immunoreactivity (5%/4% vs. 19%/12%, p = 0.001) compared to mature KAs. These findings indicate a role for mitotic cyclins in the evolution of both SCC and KA. The overlapping patterns of expression for these mitosis-related antigens suggest that KAs represent a variant of SCC that exhibit an overwhelming but not absolute tendency to involute.

Background: Telomerase is a ribonucleoprotein that maintains telomeric base pair repeats at the ends of mammalian chromosomes during DNA replication. Telomerase is expressed in various human tumors, some normal tissues, and immortalized cell lines. The assay of telomerase activity has potential as an adjunct for cancer detection in cytologic fluids., Methods: Twenty-four unfixed cytologic fluids, including 13 ascitic fluids, 7 pleural fluids, 3 pelvic washings, and 1 bronchial washing, were prepared for polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (Oncor, Inc., Gaithersburg, MD). Telomerase activity was determined by PCR. The presence of a ladder of products with 6 base pair increments, separated by polyacrylamide gel electrophoresis and detected by phosphoimaging, was considered a positive result. Results were compared with cytologic evaluation of alcohol fixed, Papanicolaou stained smears., Results: Of the 14 cytologically malignant specimens, 11 (79%) contained detectable telomerase activity. Two cytologically malignant samples could not be evaluated for telomerase activity due to the presence of inhibitory substances of PCR reaction. Of the 10 cytologically negative specimens, 1 (10%) was positive for telomerase activity; this specimen was from a patient with history of both endometrial and lung carcinomas., Conclusions: Telomerase activity can be detected in malignant cytologic specimens and thus has potential as a diagnostic adjunct in cytopathology.

Background: In this study, the authors evaluated the prognostic significance of the expression of nucleolar antigen p120, along with other cell proliferation-associated proteins, in prostate adenocarcinomas (PACs) and compared the results with previously reported data on p34cdc2 cyclin-dependent kinase (p34 cdk)., Methods: Archival sections from 132 PACs were immunostained with monoclonal antibodies against p120, cyclin A, cyclin B1, Ki-67, and proliferating cell nuclear antigen (PCNA). The DNA content of each tumor was determined by the Feulgen method using image analysis. The immunohistochemistry (IHC) results were correlated with tumor grade, stage, margin positivity, metastasis, ploidy, and postsurgical disease recurrence., Results: The overall positivity for the various proteins follows: p120, 36%; cyclin A, 35%; cyclin B1, 43%; Ki-67, 46%; and PCNA, 32%. p120 correlated with grade (P = 0.004), stage (P = 0.01), ploidy (P = 0.02), margin positivity (P = 0.03), and metastasis (P = 0.004). Cyclin B1 correlated with ploidy (P = 0.04) and grade (P = 0.05), Ki-67 with grade (P = 0.02) and margins (P = 0.03), and PCNA with grade (P = 0.01). Significant coexpression among these proteins was noted, as was a significant association between the expression of these markers and that previously reported for p34 cdk. In univariate analysis, p120 (P = 0.01), cyclin A (P = 0.01) and p34 cdk (P = 0.002) correlated with disease recurrence. In multivariate analysis of all these proteins, only p34 cdk independently predicted postsurgical recurrence (P = 0.05)., Conclusions: Nucleolar antigen p120 expression appears to be an additional marker of aggressiveness in PACs. The significant coexpression of the various cell cycle regulatory proteins support their collective role in tumor cell proliferation, with p34 cdk positivity being an independent predictor of postsurgical recurrence.

Background: In vitro studies have shown an antiproliferative effect of tumor necrosis factor (TNF) against various nonsmall cell lung carcinoma (NSCLC) cell lines. However, clinical trials of combined interleukin-2 and TNF-alpha in patients with advanced NSCLC have demonstrated both conflicting and disappointing results., Methods: Immunohistochemical (IHC) staining was performed on formalin fixed, paraffin embedded tissues from 39 bronchogenic adenocarcinomas and 32 squamous cell carcinomas using polyclonal antibodies against TNF-alpha, TNF-beta, TNF-R1, and TNF-R2 proteins. IHC positivity was correlated with tumor stage, grade, and patient survival., Results: Significant coexpression of TNF-alpha, TNF-beta, TNF-R1, and TNF-R2 was observed in NSCLC (significance range, P < 0.001-0.02). Although immunoreactivity for TNFs remained high in all tumor stages, a loss of TNF-R expression was found in advanced NSCLC (P < 0.006 for TNF-R1 and P < 0.003 for TNF-R2), suggesting down-regulation of TNF-Rs in the process of tumor progression. When all stages were considered together, immunoreactivity for TNF-beta(P < 0.001), TNF-R1, and TNF-R2 (both P < 0.001) significantly correlated with favorable outcome in univariate analysis. However, when stages were studied separately, an association between immunopositivity for TNF-Rs and favorable prognosis was found only in NSCLC without distant metastasis (P < 0.04 and P < 0.005 for TNF-R1 and TNF-R2 in Stage I [according to the American Joint Committee on Cancer staging system] disease, and P < 0.03 and P < 0.02 for TNF-R1 and TNF-R2 in Stage III disease). On multivariate analysis, increased expression of TNF-R1 (P < 0.003) and TNF-R2 (P < 0.001) as well as tumor stage (P < 0.001) independently predicted favorable outcome in patients with NSCLC., Conclusions: Although NSCLC exhibits strong coexpression of TNF-alpha, TNF-beta, TNF-R1, and TNF-R2, there is a loss/down-regulation of TNF receptors in high stage tumors. TNF-R1 and TNF-R2 positivity independently predicts favorable outcome in NSCLC, particularly in tumors with no clinically distant metastasis. The current study supports a role for TNFs and their receptors in the evolution and progression of NSCLC.

Background: Cyclin-dependent kinases (CDK) and cyclins constitute the subunits of the maturation-promoting factor that controls the process of cell division. High levels of these proteins have been reported in human malignancies of the stomach, colon, breast, and lung, and have been implicated in aberrant cell division and dysregulated tumor growth., Methods: p34cdc2 CDK and cyclin D1 (D1) protein expression were evaluated in 140 radical prostatectomy specimens harboring adenocarcinoma (PAC), using the respective monoclonal antibodies on archival tissue sections. In each case, slides stained with hematoxylin and eosin were examined for evaluation of Gleason's grade and pathologic stage. The DNA content of the tumors was determined by the Feulgen method with the CAS200 Image Analyzer (Cell Analysis Systems, Lombard, IL). Nuclear immunoreactivity for the two proteins was semiquantitatively scored, and results were correlated with Gleason's grade, stage, ploidy, metastatic status, and disease recurrence after radical prostatectomy., Results: p34cdc2 was expressed in 84 of 140 PACs (60%) and correlated with high Gleason's grade (P = 0.0001), advanced pathologic stage (P = 0.01), nondiploid DNA content (P = 0.0001), and metastases (P = 0.04). On multivariate analysis using the Cox proportional hazards model, p34cdc2 immunoreactivity (P = 0.0001) and high Gleason's grade (P = 0.01) each independently predicted disease recurrence. When tumors were of low Gleason's grade and lacked p34cdc2 expression, 4 of 39 PACs (10%) recurred, as compared with 18 of 47 (38%) that recurred when tumors were of high Gleason's grade and expressed p34cdc2 protein. D1 was positive in 31 of 140 PACs (22%) and showed a trend (P = 0.07) of high Gleason's grade, but it did not reach statistical significance with any of the prognostic variables. In the majority of PACs expressing both p34cdc2 and D1 proteins, the adjacent benign prostate acini showed focal, scattered nuclear positivity of the basal and secretory epithelial cells., Conclusions: p34cdc2 is expressed in a majority of PACs and correlates with high Gleason's grade, advanced pathologic stage, nondiploid DNA content, and metastases. On multivariate analyses high Gleason's grade and p34cdc2 immunoreactivity predict disease recurrence independently of the pathologic stage. Thus, p34cdc2 appears to play a critical role in the evolution, proliferation, and spread of PACs and may be of prognostic value when applied to initial prostate tissue samples taken by needle biopsy.

Background: Although nuclear grooves and inclusions are considered to be characteristic cytologic features of thyroid papillary carcinoma, a variety of other thyroid lesions may on occasion display these features in fine-needle aspiration specimens., Methods: The authors evaluated the immunocytochemical staining of 16 fine-needle aspirations of thyroid papillary carcinoma and 14 aspirations of thyroid lesions confirmed to be other than papillary carcinoma but that included cells with nuclear grooving and/or inclusions, comprised of multinodular goiter (four cases), follicular adenoma (two cases), Hurthle cell adenoma (two cases), pure thyroiditis (three cases), and thyroiditis with nodular hyperplasia (three cases). CD44 previously has been shown to be selectively expressed in thyroid papillary carcinoma., Results: Of 16 surgically confirmed cases of thyroid papillary carcinoma featuring nuclear grooves and inclusions on fine-needle aspiration, 14 (88%) stained intensely for CD44 in a membranous pattern. Of the 14 nonpapillary thyroid carcinoma cases, only 1 (7%), a Hürthle cell adenoma, featured membranous CD44 staining. The difference in the proportion of cases with CD44 staining between the two groups was statistically significant (chi-square test, P < 0.001)., Conclusions: The authors conclude that immunostaining for CD44 can readily be performed on thyroid fine-needle aspiration specimens and that, for specimens featuring nuclear grooves and inclusions, the presence or absence of staining for CD44 may be of value in the distinction between thyroid papillary carcinoma and other lesions that may share some of the cytologic features of papillary carcinoma.

Background: HER-2/neu gene amplification, established as a prognostic factor in breast carcinoma and other cancers, has not been correlated with outcome in prostate carcinomas (PCs)., Methods: HER-2/neu gene amplification was determined by automated fluorescence in situ hybridization (FISH) using a unique sequence cosmid probe on 113 formalin fixed, paraffin embedded 4-microns tissue sections and the results compared with tumor grade, DNA ploidy, HER-2/neu protein expression by immunohistochemistry (IHC), serum prostate specific antigen, pathologic stage, and postoperative disease recurrence (mean follow-up of 44 months)., Results: HER-2/neu gene amplification by FISH (41% of PCs) correlated with tumor grade (P = 0.001) and DNA ploidy status (P = 0.0003). HER-2/neu protein overexpression by IHC (29% of PCs) correlated with grade (P = 0.03), but not with DNA ploidy. A trend for similar HER-2/neu status in each PC by IHC and FISH did not reach statistical significance (P = 0.25). On univariate analysis, HER-2/neu amplification by FISH (P = 0.029), tumor grade (P = 0.013), and DNA ploidy (P = 0.016) correlated with postoperative disease recurrence. HER-2/neu expression by IHC did not correlate with outcome. On multivariate analysis, grade (P = 0.0001) and ploidy (P = 0.001) were independent outcome predictors; HER-2/neu amplification by FISH reached near-independent significance (P = 0.125)., Conclusions: HER-2/neu gene amplification by FISH on archival PCs significantly correlates with grade and DNA ploidy status, is more sensitive than IHC in detecting HER-2/neu gene abnormalities, predicts postoperative disease recurrence, and may prove important in planning therapy for patients with prostate carcinoma.

Background: CD44, a transmembrane protein, is associated with cell-cell and cell-matrix interaction and with tumor growth and metastasis. Expression of both standard form and variant isoforms of CD44 protein has been associated with aggressive behavior and metastasis in various tumors, but has not been characterized in prostate adenocarcinoma (PAC)., Methods: The expression of CD44 standard (CD44s) and splice variant v3, v4/5, v6, v7/8, and v10 proteins were studied in 109 PACs and correlated with tumor grade, DNA ploidy, and mRNA levels. Monoclonal antibodies against the various CD44 proteins were applied to microwave irradiated, formalin fixed, paraffin embedded sections. The DNA content of the tumors was evaluated by the Feulgen method with the CAS200 Image Analyzer. Total RNA exhibiting 18s and 28s bands was derived from two benign prostatic tissues and 5 PACs exhibiting decreased levels of CD44 protein by immunohistochemistry. The RNA was analyzed with reverse transcriptase polymerase chain reaction using CD44 specific primers., Results: The basal cells of the benign prostatic acini revealed uniform membranous staining for CD44s, v3, and v6 in 95-97% of cases. Similar staining was observed for v4/5, v7/8, and v10 in 40%, 30%, and 2% of cases, respectively. Secretory epithelial cells of the benign prostatic acini showed predominant expression of CD44s (97% of cases). Staining for CD44 variant proteins (v3, v4/5, v6, v7/8, and v10) in this location ranged from 9-22% of cases. Approximately 70% of the PACs showed significant loss of CD44s expression, which correlated with high tumor grade (Gleason > or = 7) (P = 0.01) and aneuploid status (P = 0.002). In 93-98% of the PACS, there was a complete lack of membranous expression for all CD44 variant isoforms. The metastatic PACS did not show preferential expression of either the standard form or any variant isoform. The cDNA from the normal prostates yielded a prominent CD44 standard form polymerase chain reaction product at 482 base pair (bp) and variant isoforms at approximately 650 and 850 bp. No CD44 products could be amplified from the subset of five PAC cDNAs, even when present at four-fold excess., Conclusions: PACS exhibit down-regulation of CD44 protein expression, which correlates with high tumor grade and aneuploidy. v6 and v3 isoforms were preferentially expressed in the basal cells of benign prostatic acini. Based on a subset of cases, loss of CD44 protein expression is associated with decreased abundance of CD44 mRNA.

Background: DNA ploidy determination of carcinomas in radical prostatectomy specimens has shown significant correlation with patient outcome, but the predictive value of ploidy status of cancers obtained by transrectal ultrasound-guided needle biopsies has not been studied extensively., Methods: Eighty-nine paired needle biopsy specimens (NBX) and radical prostatectomy (RPX) specimens from patients with early clinical stage (A2-B2) prostate cancer were evaluated for DNA content by image analysis of Feulgen stained tissue sections. Findings were compared with Gleason grading on the same specimens by univariate and multivariate analyses for prediction of local tumor invasion, metastasis, disease recurrence, and serum prostate specific antigen concentration during a 0.9-6.0 year clinical follow-up period., Results: There was excellent correlation of ploidy status between NBX and RPX specimens (P < 0.0001); NBX and RPX grades did not correlate. On RPX specimens, aneuploid status correlated with high tumor grade (P < 0.0005). Aneuploidy in NBX specimens was associated with a twofold higher rate of extracapsular spread (ECS) (P = 0.04). Aneuploid NBX tumors featured a tenfold greater frequency of metastasis than did diploid NBX tumors (P < 0.005). Radical prostatectomy grade correlated with ECS (P < 0.001) and presence of metastatic disease (P = 0.04). On multivariate logistic regression analysis, aneuploidy in both NBX and RPX specimens was the most significant variable and independently predicted the presence of metastasis (P = 0.006 for NBX; P = 0.028 for RPX). Tumor grade of NBX and RPX specimens did not independently predict metastatic disease or disease recurrence, but RPX grade was associated independently with ECS (P = 0.005). Aneuploid NBX tumors recurred after RPX three times more often than did diploid cases, which was significant on univariate (P < 0.001) and multivariate (P = 0.018) analyses using the Cox proportional hazards model. There was no correlation with NBX or RPX Gleason score and disease recurrence. Preoperative serum PSA concentration did not correlate with tumor grade or ploidy status, but on multivariate analysis, when paired with ploidy status, independently contributed to the propensity for ECS, metastasis, and disease recurrence., Conclusions: DNA content analysis of early clinical stage prostate carcinoma needle biopsy specimens by image analysis directly correlates with radical prostatectomy specimen ploidy status and is associated independently, with the presence of metastasis, postprostatectomy disease recurrence, and ECS. Needle biopsy tumor grading did not correlate with prostatectomy grade and did not predict disease outcome accurately.

Background: Genetic changes in the development of endometrial carcinoma have not been characterized, and little is known of tumor or metastatic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tumor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm23-H1., Methods: The status of the p53 gene was studied by immunohistochemistry of formalin-fixed paraffin-embedded biopsy samples from 72 patients with atypical endometrial hyperplasia or endometrioid carcinoma who underwent hysterectomy immediately after biopsy and from 5 patients with benign endometria. A search for loss of heterozygosity (LOH) of the nm23 gene after DNA extraction from frozen tissues and hybridization with nm23-H1 cDNA specific probe was made in 10 endometrial carcinomas. Rb gene status was evaluated by image analysis quantification of immunoreactive retinoblastoma protein in frozen sections of 10 carcinomas and 2 benign endometria., Results: p53 expression was low in all benign endometria, but high expression was found in 2 (15%) of 13 atypical hyperplasias and in 23 (39%) of 59 carcinomas. High levels of p53 expression in endometrioid carcinoma correlated with the spread of disease outside of the uterus and by logistic regression, the presence of squamous differentiation, nuclear grade, and high p53 expression in the biopsy all independently correlated with spread of disease outside of the uterus. Although 7 of the 10 carcinomas studied were informative, LOH for the nm23 gene was not seen in any, including a site of metastasis. Rb protein expression in endometrial carcinoma was similar to expression in benign endometria., Conclusions: Although this study found no evidence of nm23-H1 gene alteration or alterations in Rb protein levels in endometrial carcinoma, high expression of p53 protein was sporadically identified in biopsy specimens of atypical hyperplasia and frequently found in endometrioid carcinomas. Determination of p53 expression in combination with the presence or absence of squamous differentiation and nuclear grade in biopsy material may help predict spread of endometrioid carcinoma outside the uterus and facilitate therapeutic planning before hysterectomy.

Background: Recent advances in the early detection of prostatic adenocarcinoma have stimulated interest in the development of techniques for determining metastatic potential., Methods: One hundred cases of adenocarcinoma, including 66 biopsy and radical prostatectomy specimens; 20 biopsies alone; and 14 transurethral resection specimens, were evaluated for Gleason tumor grade, DNA content and HER-2/neu expression. DNA content was determined on Feulgen-stained touch preparations and tissue sections (18 cases) or tissue sections alone. HER-2/neu expression level was determined by image-analysis-assisted quantitative immunocytochemistry., Results: Tumor grade and ploidy status were independent significant predictors of metastasis. HER-2/neu overexpression was found in 16 (16%) of the 100 cases and significantly correlated with high-tumor grade and aneuploid status, but was not of independent value in the prediction of metastasis., Conclusions: HER-2/neu overexpression is not uncommon in prostatic adenocarcinoma and is associated with high-tumor grade, abnormal DNA content, and distant metastasis. Tumor grade and DNA ploidy values are of the greatest value in determining the presence of metastasis.

The authors present their 1-year experience with the use of 3DFT, time-of-flight MR angiography for the evaluation of vascular diseases of the head and neck. Their experience with over 150 patients indicates that this examination may be performed in conjunction with standard spin-echo imaging with only a minimal increase in patient examination time. This combined examination is most applicable to atherosclerotic disease of the carotid bifurcation, arterial occlusions of the primary and secondary branches of the intracranial circulation (particularly in pediatric patients such as those following ECMO or with sickle cell anemia), and patients with saccular berry aneurysms. This type of static, angiographic technique adds little to standard spin-echo imaging in patients with arteriovenous fistulae, neoplasms, and giant intracranial aneurysms. Limitations of the present technique include the inability to visualize slow flow lesions (e.g., giant aneurysms) and selected high flow states (arteriovenous fistulae, some severe stenoses).

The nutritional efficacy and hepatic changes in rats given a total parenteral nutrition (TPN) solution consisting of 4.25% amino acids and 25% dextrose by intragastric, intravenous, or prehepatic routes were studied over a 4-day period. Rats fed Purina Chow or given intragastric TPN maintained body weight and showed no appreciable fatty change of liver. In contrast, weight loss, hepatomegaly, and a 37% increase in liver lipid content were observed in rats given intravenous TPN and a 60% increase after prehepatic TPN. Approximately half the rats given intravenous or prehepatic TPN developed fatty changes in the liver. Serum albumin concentration and hepatic protein content were not improved after prehepatic TPN. Serum SGOT and SGPT were elevated in rats given prehepatic TPN only. Prehepatic TPN may result in hepatic injury and offers no apparent benefit over conventional intravenous TPN in rats.

An unusual form of squamous cell carcinoma of the tongue is reported, the "de novo" submucosal evolution of which is unique. Histologic definition of this malignancy and its distinction from clinically similar benign and malignant conditions are detailed through a brief review of the relevant differential diagnoses. The importance of circumspect diagnostic reassessment when the clinical behavior of a lesion contradicts apparent histologic benignancy is emphasized and treatment inferences are drawn.