Expanding conceptualizations of harm reduction: results from a qualitative community-based participatory research study with people who inject drugs.

BACKGROUND: The perspectives of people who use drugs are critical in understanding why people choose to reduce harm in relation to drug use, what practices are considered or preferred in conceptualizations of harm reduction, and which environmental factors interfere with or support the use of harm reduction strategies. This study explores how people who inject drugs (PWID) think about harm reduction and considers the critical imperative of equity in health and social services delivery for this community. METHODS: This community-based participatory research study was conducted in a Canadian urban centre. Using a peer-based recruitment and interviewing strategy, semi-structured qualitative interviews were conducted by and with PWID. The Vidaview Life Story Board, an innovative tool where interviewers and participant co-construct a visual "life-scape" using a board, markers, and customized picture magnets, was used to facilitate the interviews. The topics explored included injection drug use and harm reduction histories, facilitators and barriers to using harm reduction strategies, and suggestions for improving services and supports. RESULTS: Twenty-three interviews with PWID (14 men and 9 women) were analysed, with a median age of 50. Results highlighted an expanded conceptualization of harm reduction from the perspectives of PWID, including motivations for adopting harm reduction strategies and a description of harm reduction practices that went beyond conventional health-focused concerns. The most common personal practices that PWID used included working toward moderation, employing various cognitive strategies, and engaging in community activities. The importance of social or peer support and improving self-efficacy was also evident. Further, there was a call for less rigid eligibility criteria and procedures in health and social services, and the need to more adequately address the stigmatization of drug users. CONCLUSIONS: These findings demonstrated that PWID incorporate many personal harm reduction practices in their daily lives to improve their well-being, and these practices highlight the importance of agency, self-care, and community building. Health and social services are needed to better support these practices because the many socio-structural barriers this community faces often interfere with harm reduction efforts. Finally, "one size does not fit all" when it comes to harm reduction, and more personalized or de-medicalized conceptualizations are recommended.

Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases.

BACKGROUND: Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor ß, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. METHODS: This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. RESULTS: The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. CONCLUSIONS: This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.

Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). METHODS: The study, conducted prospectively during 2009-2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6-8 weeks before 90Y treatment. Safety and tolerability were assessed. RESULTS: Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. CONCLUSIONS: Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit.

Multidisciplinary department of "Return to Work After a Cancer": a French experience of support groups for vocational rehabilitation.

This qualitative pilot exploratory study focuses on support groups for vocational rehabilitation after cancer implemented in a French and innovative multidisciplinary department of "Return to Work after a Cancer." Sixty-three patients were invited to participate to constitute two support groups of 20 participants. Questionnaires are sent to assess their benefit according to the participants' point of view. For 58% of participants, support groups helped the return to work, and for 70% it provided personal, family, and relational support. Support groups are a relevant response to expectations and specific issues of patients experiencing return to work after cancer.

The role of interventional radiology in the management of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (hcc) is one of the most common causes of cancer-related death worldwide. Overall, liver transplantation and resection are the only available treatments with potential for cure. Various locoregional therapies are widely used to manage patients with advanced hcc or as a bridging therapy for patients with early and intermediate disease. This article reviews and evaluates the role of interventional radiology in the management of such cases by assessing various aspects of each method, such as effect on rates of survival, recurrence, tumour response, and complications. METHODS: A systemic search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of Systematic Reviews retrieved all related scientific papers for review. RESULTS: Needle core biopsy is a highly sensitive, specific, and accurate method for hcc grading. Portal-vein embolization provides adequate expansion of the future liver remnant, making more patients eligible for resection. In focal or multifocal unresectable early-stage disease, radiofrequency ablation tops all other thermoablative methods. However, microwave ablation is preferred in large tumours and in patients with Child-Pugh B disease. Cryoablation is preferred in recurrent disease and in patients who are poor candidates for anesthesia. Of the various transarterial modalities-transarterial chemoembolization (tace), drug-eluting beads, and transarterial radio-embolization (tare)-tace is the method of choice in Child-Pugh A disease, and tare is the method of choice in hcc cases with portal vein thrombosis. CONCLUSIONS: The existing data support the importance of a multidisciplinary approach in hcc management. Large randomized controlled studies are needed to provide clear indication guidelines for each method.

CD28 signals through acidic sphingomyelinase.

T cell receptor recognition of antigen can lead either to T lymphocyte differentiation and proliferation or to a state of unresponsiveness, which is dependent on whether appropriate costimulatory signals are provided to the mature T cell. We have investigated a novel intracellular signaling pathway provided by the costimulatory molecule CD28. CD28 engagement triggers the activation of an acidic sphingomyelinase (A-SMase), which results in the generation of ceramide, an important lipid messenger intermediate. A-SMase activation by CD28 occurred in resting as well as in activated primary T cells or leukemic Jurkat cells. In contrast, ligation of either CD3 or CD2 did not result in A-SMase activation. Overexpression of recombinant A-SMase in Jurkat T cells substituted for CD28 with regard to nuclear factor-kB activation. These data suggest that CD28 provides an important costimulatory signal by activation of an acidic sphingomyelinase pathway.

Safety of dry needling to the upper lumbar spine: a pilot cadaver study.

Objective: When inserting a dry needle laterally into the upper lumbar spine (L1-L3) there is an increased risk of piercing the kidney; therefore, the objective of this study was to determine a zone of safety for practitioners to needle in the upper lumbar spine.Methods: Ten cadavers were screened for inclusion. L1 spinous process was identified and confirmed with ultrasound imaging. A digital caliper was used to measure laterally at 1.5 cm, 2.0 cm, and 2.5 cm. Dry needles were inserted maximally at each point and a binary decision, yes or no, was made to determine if bony contact was made. Needle depth and abdominal width measurements were also recorded. Safety of the dry needling procedure was interpreted as such if bony contact was made by the needle. If bony contact was made, then it was assumed that the needle cannot advance further into pleura or kidney.Results: Forty-four percent of needles did not make bony contact at 2.5 cm lateral of the L1 spinous process, whereas 22% did not make bony contact at 1.5 cm and 2.0 cm. There was a weak to moderate negative correlation between abdominal width measurements and needle depth at 1.5 cm (-0.48) and 2.0 cm (-0.45), and at 2.5 cm (-0.39).Conclusion: A safety zone of needling less than 2.5 cm is likely safe, but needs to be confirmed with future study. Dry needling 2.5 cm lateral appears more risky due to the higher frequency of not contacting a bony backdrop.

Optimized nerve block techniques while performing percutaneous hepatic ablation: Literature review and practical use.

Percutaneous image guided thermal ablation has become a cornerstone of therapy for patients with oligometastatic disease and primary liver malignancies. Evolving from percutaneous ethanol injection (PEI), thermal ablation utilizing radiofrequency ablation (RFA) and microwave ablation (MWA) have become the standard approach in the treatment of isolated lesions that fit within the size criteria for curative intent therapy (typically 3-4cm). With the evolution of more intense thermal ablation, such as MWA, the dramatic increase in both the size of ablation zone and intensity of heat generation have extended the limits of this technique. As a result of these innovations, intra-procedural and post-procedural pain have also significantly increased, requiring either higher levels of intravenous sedation or, in some institutions, general anesthesia. In addition to the increase in therapeutic intensity, the use of intravenous sedation during aggressive ablation procedures carries the risk of over-sedation when the noxious insult (i.e. the ablation) is removed, adding further difficulty to post-procedural recovery and management. Furthermore, high subdiaphragmatic lesions become challenging in this setting due to issues relating to sedation and compliance with breath hold/breathing instructions. Although general anesthesia may mitigate these complications, the added resources associated with providing general anesthesia during ablation is not cost effective and may result in substantial delays in treatment. The reduction of Aerosol Generating Medical Procedures (AGMP), such as intubation due to the COVID-19 Pandemic, must also be taken into consideration. Due to the potential increased risk of infection transmission, alternatives to general anesthesia should be considered when safe and possible. Upper abdominal regional nerve block techniques have been used to manage pain related to trauma, surgery, and cancer; however, blocks of this nature are not well described in the interventional radiology literature. The McGill University group has developed experience in using such blocks as splanchnic, celiac and hepatic hilar nerve blocks to provide peri-procedural pain control [1]. Since incorporating these techniques (along with hydrodissection with tumescent anesthesia), we have also observed in our high volume ablation center a dramatic decrease in the amount of sedatives administered during the procedure, a decrease in patient discomfort during localization and ablation, as well as decreased pain post-procedure. Faster time to discharge and overall reduction in room procedural time serve as added benefits. The purpose of this publication is to outline and illustrate the practical application and use of nerve block/regional anesthesia techniques with respect to percutaneous hepatic thermal ablation.

Predicting inferior vena cava (IVC) filter retrievability using positional parameters: A comparative study of various filter types.

PURPOSE: To compare changes in inferior vena cava (IVC) filter positional parameters from insertion to removal and examine how they affect retrievability amongst various filter types. MATERIALS AND METHODS: A total of 447 patients (260 men, 187 women) with a mean age of 55 years (range: 13-91 years) who underwent IVC filter retrieval between 2007-2014 were retrospectively included. Post-insertion and pre-retrieval angiographic studies were assessed for filter tilt, migration, strut wall penetration and retrieval outcomes. ANCOVA and multiple logistic regression models were used to analyze factors affecting retrieval success. Pairwise comparisons between filter types were performed. RESULTS: Of 488 IVC filter retrieval attempts, 94.1% were ultimately successful. The ALN filter had the highest mean absolute value of tilt (5.6 degrees), the Optease filter demonstrated the largest mean migration (-8.0mm) and the Bard G2 filter showed highest mean penetration (5.2mm). Dwell time of 0-90 days (OR, 11.1; P=0.01) or 90-180 days (OR, 2.6; P=0.02), net tilt of 10-15 degrees (OR 8.9; P=0.05), caudal migration of -10 to 0mm (OR, 3.46; P=0.03) and penetration less than 3mm (OR, 2.6; P=0.01) were positive predictors of successful retrievability. Higher odds of successful retrieval were obtained for the Bard G2X, Bard G2 and Cook Celect when compared to the ALN and Cordis Optease filters. CONCLUSION: Shorter dwell time, lower mean tilt, caudal migration and less caval wall penetration are positive predictors of successful IVC filter retrieval.

MAPK specificity in the yeast pheromone response independent of transcriptional activation.

The mechanisms whereby different external cues stimulate the same mitogen-activated protein kinase (MAPK) cascade, yet trigger an appropriately distinct biological response, epitomize the conundrum of specificity in cell signaling. In yeast, shared upstream components of the mating pheromone and filamentous growth pathways activate two related MAPKs, Fus3 and Kss1, which in turn regulate programs of gene expression via the transcription factor Ste12. As fus3, but not kss1, strains are impaired for mating, Fus3 exhibits specificity for the pheromone response. To account for this specificity, it has been suggested that Fus3 physically occludes Kss1 from pheromone-activated signaling complexes, which are formed on the scaffold protein Ste5. However, we find that genome-wide expression profiles of pheromone-treated wild-type, fus3, and kss1 deletion strains are highly correlated for all induced genes and, further, that two catalytically inactive versions of Fus3 fail to abrogate the pheromone-induced transcriptional response. Consistently, Fus3 and Kss1 kinase activity is induced to an equivalent extent in pheromone-treated cells. In contrast, both in vivo and in an in vitro-reconstituted MAPK system, Fus3, but not Kss1, exhibits strong substrate selectivity toward Far1, a bifunctional protein required for polarization and G(1) arrest. This effect accounts for the failure to repress G(1)-S specific transcription in fus3 strains and, in part, explains the mating defect of such strains. MAPK specificity in the pheromone response evidently occurs primarily at the substrate level, as opposed to specific kinase activation by dedicated signaling complexes.

Development of a database: DACTARI for a radiotoxic element ranking methodology.

Dosimetric impact studies aim at evaluating potential radiological effects of chronic or acute releases from nuclear facilities. A methodology for ranking radionuclides (RN) in terms of their health-related impact on the human population was first developed at CEA with specific criteria for each RN that could be applied to a variety of situations. It is based, in particular, on applying physico-chemical criteria to the complete RN inventory (present in the release or in the source term) and on applying norms related to radiation protection and chemical toxicology. The initial step consisted in identifying and collecting data necessary to apply the methodology, with reference to a previous database of long-lived radionuclides (LLRN, with half-lives ranging from 30 to 10(14) y) containing 95 radionuclides. The initial results have allowed us to identify missing data and revealed the need to complete the study for both toxic and radiotoxic aspects. This led us to the next step, developing a specific database, DAtabase for Chemical Toxicity and Radiotoxicity Assessment of RadIonuclides (DACTARI), to collect data on chemical toxicity and radiotoxicity, including acute or chronic toxicity, the chemical form of the compounds, the contamination route (ingestion, inhalation), lethal doses, target organs, intestinal and maternal-foetal transfer, drinking water guidelines and the mutagenic and carcinogenic properties.

Specific soman-hydrolyzing enzyme activity in a clonal neuronal cell culture.

An enzymatic activity that specifically hydrolyzes the highly toxic organophosphorus anticholinesterase compound soman (pinacolyl methylphosphonofluoridate) has been identified and partially characterized in the clonal neuronal neuroblastoma-glioma hybrid NG108-15 cell line. Using the whole cell homogenate as the enzyme source and 1 mM substrate, the relative rate of hydrolysis of two other toxic anticholinesterase compounds sarin (isopropyl methylphosphonofluoridate) and tabun (ethyl-N-dimethyl phosphoramidocyanidate) is approximately one-tenth the rate of hydrolysis of soman, while DFP (diisopropyl phosphorofluoridate), paraoxon (p-nitrophenyl diethylphosphate), and a phosphinate PNMPP (p-nitrophenyl methyl (phenyl) phosphinate) are not hydrolyzed. Analysis of the kinetics of soman hydrolysis reveals two components of the enzyme activity with different affinities and reaction rates. Unlike previously reported enzymes of this type, this enzyme lacks chiral specificity and thus hydrolyzes both toxic and non-toxic soman stereoisomers at equal rates. The enzyme activity is stable at low temperature, found almost exclusively in the soluble fraction of these cells, and enhanced significantly by Mn2+ and by chemical differentiation of these cells in culture. The results suggest possible application of this enzyme for soman detection and/or detoxication, and use of the NG108-15 cell line to study the natural function(s) of enzymes of this type.

Effect of tamoxifen on sexual functioning in patients with breast cancer.

PURPOSE: To define the incidence of sexual dysfunction in a population of women with breast cancer treated with tamoxifen. PATIENTS AND METHODS: Breast cancer patients with a performance status of 0 to 2 who had been treated with tamoxifen for 2 to 24 months completed the following measures: the Center for Epidemiologic Studies-Depression Scale, the Sexual History Form, and the Breast Cancer Prevention Trial Symptom Checklist. Forty-nine of the participants underwent gynecologic examinations with vaginal smears for determination of estrogen effect. RESULTS: Fifty-seven women were entered onto the trial. Sexual desire, arousal, and ability to achieve orgasm were comparable to norms established in participants in the Tamoxifen Prevention Trial (National Surgical Adjuvant Breast and Bowel Project P-01). Pain, burning, or discomfort with intercourse was reported in 54% of patients and did not correlate with age, surgical treatment of the primary cancer, or chemotherapy. Estrogen effect was seen on the vaginal smears of 34 of 49 participants and was more common in older patients (P = .054). The presence of estrogen effect correlated with negative reactions during sex (P = .02) and vaginal dryness or tightness (P = .046). CONCLUSION: Women treated with tamoxifen in the adjuvant setting experienced symptoms of sexual dysfunction. The individual contributions of chemotherapy and tamoxifen to sexual dysfunction warrant prospective study.

Partial characterization of an enzyme that hydrolyzes sarin, soman, tabun, and diisopropyl phosphorofluoridate (DFP).

The properties of a rat liver enzyme that hydrolyzes organophosphorus (OP) inhibitors of cholinesterases were studied. The rates of hydrolysis of OP inhibitors were determined by continuous titration of released hydrogen ions, using a pH stat method. Centrifugation of homogenates at 205,000 g for 30 min demonstrated that the activity was in the soluble fraction. Hydrolysis of sarin, soman, and diisopropyl phosphorofluoridate (DFP), but not of tabun, was stimulated by the addition of Mn2+ and Mg2+. Hydrolysis of sarin greater than soman greater than tabun greater than DFP. Unlike other OP hydrolases that preferentially hydrolyze the non-toxic isomers of soman, this enzyme hydrolyzed all four soman isomers at approximately the same rate. This result was obtained in vitro by gas chromatographic analysis of enzyme-catalyzed soman hydrolysis and confirmed in vivo by demonstrating reduced toxicity in mice of soman partially hydrolyzed by this enzyme. Km and Vmax were determined by fitting V vs [S] to a hyperbolic function using regression analysis. Km values ranged from 1.1 mM for soman to 8.9 mM for tabun. Vmax values ranged from 54 nmol/min/mg protein for DFP to 2694 for sarin. The enzyme was stable for at least 2 months at -90 degrees but was inactivated by heating at 100 degrees for 5 min. Elution profiles from gel filtration by high pressure liquid chromatography showed that the hydrolytic activity for the OP inhibitors eluted in a single peak, suggesting that a single enzyme was responsible for the observed hydrolysis. Further purification and characterization of this enzyme should prove useful for the development of methods for detection, detoxification, and decontamination of these cholinesterase inhibitors.

Bronchial epithelial changes associated with small cell carcinoma of the lung.

From 1976 to 1991, 151 cases of small cell carcinoma of the lung were diagnosed by fiberoptic bronchoscopic biopsy at our institution. One hundred twenty-eight of 151 cases provided suitable material for the examination of the morphologic changes in the bronchial surface epithelium. Thirty-seven percent of the cases showed normal bronchial epithelium, 47% showed benign squamous metaplasia, 9% showed atypical squamous metaplasia, and 5% showed squamous cell carcinoma in situ. Immunohistochemical examination for bombesin and epidermal growth factor was performed on selected biopsy specimens. The biopsy specimens chosen for immunohistochemistry included 20 specimens that showed normal bronchial epithelium, 20 specimens with benign squamous metaplasia, 12 specimens with atypical squamous metaplasia, and seven specimens with squamous cell carcinoma in situ. All the specimens showed positive staining with anti-bombesin. With anti-epidermal growth factor 10% of biopsy specimens with normal epithelium showed positive staining. The positive reaction increased from 25% for biopsy specimens with benign squamous metaplasia to 58% for biopsy specimens with atypical squamous metaplasia and to 71% for biopsy specimens with carcinoma in situ. These findings suggest a connection between epidermal growth factor production by small cell carcinoma of the lung cells and changes in the bronchial surface epithelium.

The expression of trophoblastic cell markers by lung carcinomas.

The authors studied the expression of trophoblastic cell markers in lung carcinomas cells by immunoperoxidase staining using antibodies against three trophoblastic glycoproteins (human chorionic gonadotropin [hCG]; human placental lactogen [hPL]; pregnancy-specific beta 1-glycoprotein [SP-1]). One hundred five tissue sections from 44 lung carcinomas of various histological types were examined for positive staining with three antibodies. Hematoxylin-eosin-stained sections from the same tissue blocks were examined for the presence of tumor giant cells. The aim was to study the relationship between tumor giant cells and the trophoblastic glycoprotein expression in lung carcinomas. Small cell carcinoma (SCC) did not show any positive reaction with all three markers. Squamous cell carcinoma (SQCC) showed positive staining with hCG in 21% of cases, hPL in 28%, and SP-1 in 64%. Adenocarcinoma showed positive staining with hCG in 60% of cases, hPL in 10%, and SP-1 in 80%. Large cell carcinoma (LCC) showed positive staining with hCG in 93% of cases, hPL in 56%, and SP-1 in 93%. The positive reaction did not appear to be restricted to nor associated with the tumor giant cells. It was concluded that these trophoblastic cell markers are expressed in various types of lung carcinomas and that they are not associated with certain histological types or with tumor giant cells.

Cognitively impaired spouses as primary caregivers for demented elderly people.

OBJECTIVE: To describe problems of dementia patients whose spousal caregivers are also cognitively impaired. DESIGN: Retrospective chart review. SETTING: The geriatric assessment clinic at University of California, San Diego, which is one center for the California State sponsored Alzheimer's Disease Diagnosis and Treatment Center Program. PATIENTS: During the period from January 1992 through May 1994, 65 patients completed the assessment and met the entry criteria of being demented and having a spousal caregiver. Twelve of the spouses scored six or more error points on the Katzman Short Orientation-Memory-Concentration Test. MEASUREMENTS: Patient data included age, living situation, other caregivers, use of formal and informal support systems, profiles of medical, cognitive, and functional ability, caregivers interactions, and recommendations from the evaluation. MAIN RESULTS: Dementia patients with cognitively impaired spouses utilized fewer community resources (P = .021) and experienced difficulty with medication compliance (P = .041) more often than those with cognitively normal spousal caregivers. CONCLUSIONS: Older caregivers of patients suffering from dementia should be screened for cognitive problems.

Tubular breast cancer experience at Washington University: a review of the literature.

Our objective was to review the presentation and management of patients with tubular breast cancer treated at Barnes-Jewish Hospital and compare our findings with the available literature. Of 3908 cases of breast cancer treated at our institution between 1986 and 1995, the incidence of tubular breast cancer at Barnes-Jewish Hospital was 1.25%. We reviewed the breast cancer risks, initial presentation, treatment, and outcome of 39 women with 40 tubular breast cancers and compared our series with others in the literature. The mean patient age was 67 years, which is older than most other series. Twenty-nine of the 39 cancers (74%) were detected by screening mammography; the remainder presented with a palpable breast mass. The mean tumor size was 8 mm (range, 1-60 mm). Twenty-three of 25 tumors were ER+ (92%) and none had axillary nodal involvement. Bilateral breast cancer developed in 3 patients (8%). An additional 500 cases of tubular breast cancer have been described in the literature. When the component of the invasive tumor is > 75% tubular carcinoma, most patients present with early-stage disease that is ER+ in 47 of 56 tumors (84%). The natural history is indolent and metastases are rare. Bilateral breast cancer developed in 58 of the 540 cases (11%), 4 of which were tubular carcinomas. Local recurrences developed in 9 of 29 patients (31%) treated by excision alone. The role of tamoxifen has not been determined. Given the available data, the initial surgical staging and management of tubular carcinoma should be identical to other invasive histologies.

Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group.

Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytology of angiosarcoma. Findings in fourteen fine-needle aspiration biopsy specimens and one pleural fluid specimen.

We report the cytologic features of 15 cases of angiosarcoma from various sites and include 14 fine-needle aspiration (FNA) biopsy specimens and 1 pleural fluid specimen. Six were initial diagnoses with histologic confirmation; an additional case in the liver was an initial diagnosis without tissue confirmation. One case represented lymph node metastasis from a primary prostatic epithelioid angiosarcoma. In 10 cases, immunohistochemical staining for factor VIII-related antigen, CD34, CD31, or Ulex europaeus agglutinin I was performed on the cytology or histology specimen. The aspirates varied in cellularity, and the degree of nuclear atypia ranged from relatively bland in a case of low-grade angiosarcoma of the prostate to highly pleomorphic in a lymph node metastasis from a facial cutaneous angiosarcoma. Vasoformative features such as intracellular RBCs, well-formed vessels, attempts at microacinar/lumen formation, and intracytoplasmic lumens were variably present. The background was bloody in all specimens, with necrosis in rare cases. This cytologic series emphasizes that the cytologic features are heterogeneous but that the diagnosis can be suggested by fine-needle aspiration (FNA) when vasoformative features are present. The diagnosis can be made conclusively by FNA with immunocytochemical confirmation of endothelial differentiation.