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Biomedical subjects

W Blumenfeld

Publications and source records attributed to W Blumenfeld.

At least 19 recordsLinked to original sources
PubMed2000

The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter.

PURPOSE: Fine-needle aspiration biopsy (FNAB) is a commonly performed procedure used in the evaluation of solitary thyroid nodules, in which the risk of malignancy is approximately 5% in most patients. Recently, the use of ultrasound (US) guidance in FNAB has been shown to enhance the diagnostic efficacy of this procedure. However, the risk of malignancy in thyroid nodules occurring within a multinodular goiter (MNG) has not been completely clarified, nor has the optimal means of investigating such nodules using FNAB. SUBJECTS AND METHODS: We performed a retrospective study of all patients seen over a 4-year period with a MNG that had one or more nodules who underwent FNAB under US guidance. The results from the history and physical examination, thyroid function and antibody tests, radionuclide studies, thyroid sonogram, cytology of aspirated nodules, and surgical pathology were recorded and analyzed. RESULTS: A total of 93 nodules were aspirated in 61 patients with MNG. Adequate material was obtained in 96% of aspirates on the first attempt. Sixty-seven aspirates in 44 patients yielded benign cytology and 22 aspirates in 15 patients yielded suspicious cytology. All patients with suspicious cytology underwent thyroid surgery. Thyroid cancer was found in 5 of these nodules, including 4 cases of papillary cancer and 1 case of Hürthle cell cancer, and 1 additional patient had occult papillary cancer discovered. The overall malignancy rate in thyroid nodules among the patients with MNG was approximately 5%. CONCLUSIONS: FNAB under US guidance is a useful diagnostic modality in the evaluation of thyroid nodules in selected patients with MNG. Because the risk of thyroid malignancy in these nodules is comparable to that which exists in solitary thyroid nodules, the possibility of thyroid malignancy should be considered in all patients with MNG.

Adenocarcinoma, Follicular↗
PubMed1999

Utility of cytokeratin 7 and 20 subset analysis as an aid in the identification of primary site of origin of malignancy in cytologic specimens.

This study was undertaken to assess the utility of combined cytokeratin (CK) 7/20 immunoprofile determination in malignant cytologic cell blocks as an aid to the identification of tumor primary site of origin. Fifty-one cases in which CK 7/20 immunocytochemistry was performed as part of the initial workup were retrieved. Their contribution to the final cytologic diagnosis of tumor primary site of origin was analyzed. CK reactivity patterns were 7+/20- (n = 34), 7-/20+ (n = 9), 7-/20- (n = 7), and 7+/20+ (n = 1). The CK 7+/CK 20- immunophenotype was the most common one obtained, and due to its wide expression in a number of common carcinomas, the least informative. The second most common immunophenotype was CK 7-/20+, which is associated with colorectal origin, and as such was very useful when obtained. The CK immunoprofile was more useful in the setting of a prior carcinoma, being a major diagnostic determinant in 13 cases (55%) from group 1 (those with a prior history of malignancy), compared to 8 cases (29%) from group 2 (those with no prior history of malignancy). In the setting of prior carcinoma, the CK immunoprofile is most useful when carcinomas under consideration have different expected immunoprofiles (e.g., CK 7+/CK20- carcinomas, including lung, breast, ovary, endometrium, and others, vs. CK 7-/CK 20+ carcinomas, primarily colorectal). When similar immunoprofiles are obtained, their usefulness is greater if they are immunoprofiles other than the most common 7+/20- pattern. Similarly, in newly diagnosed carcinomas, the CK immunoprofile either helps to narrow the differential diagnosis or points to a specific diagnosis.

Biomarkers↗
PubMed1999

Diagnostic significance of papillary structures and intranuclear inclusions in Hurthle-cell neoplasms of the thyroid.

Papillary structures and intranuclear inclusions, features which are not ordinarily associated with Hurthle-cell lesions, are occasionally noted within Hurthle-cell-rich aspirates. The diagnostic significance of these features in this setting, if any, is unknown. The purpose of this study was to determine whether these features are diagnostically useful. Specifically, since fine-needle aspiration cytology cannot distinguish between Hurthle-cell adenoma and carcinoma, we wanted to know whether the presence of either feature might aid in preoperatively assessing the likelihood of carcinoma vs. adenoma. We identified 12 cases in which a diagnosis of Hurthle-cell lesion was made by thyroid fine-needle aspiration biopsy. All cases had subsequent surgery. For every case, all cytology slides were reviewed for the presence or absence of papillary structures and intranuclear inclusions, after which the findings were correlated with the final surgical pathological diagnosis. Seven of the 12 cases had identifiable papillary structures, ranging from cases where papillary structures comprised the predominant architectural pattern to cases where rare papillary structures were found amidst a predominance of sheets and single Hurthle cells. Four of the 12 cases had intranuclear inclusions. In all cases, intranuclear inclusions were uncommon. Of 6 cases that proved to be Hurthle-cell carcinoma, 5 had papillary structures on the antecedent fine-needle aspirate cytology, and 2 had intranuclear inclusions. Of 6 cases that proved to be Hurthle-cell adenoma, 2 had papillary structures, and 2 had intranuclear inclusions. Papillary structures had a sensitivity of 83% for the presence of carcinoma, a specificity of 66%, a positive predictive value of 71%, and a negative predictive value of 80% (P = 0.2). Intranuclear inclusions had a sensitivity of 33%, a specificity of 66%, and positive and negative predictive values of 50%. Papillary structures are more common in Hurthle-cell aspirates than previously recognized. Their presence is not diagnostic of carcinoma, but neither does their absence rule out carcinoma. However, when found, the likelihood of an ultimate diagnosis of Hurthle-cell carcinoma is increased. On the other hand, intranuclear inclusions, when rare, appear to have no diagnostic value.

Adenocarcinoma↗
PubMed1996

Fine-needle aspiration as the initial diagnostic modality in malignant lung disease.

Cytologic detection of lung cancer is accepted, accurate, and time-honored. Typically, cytologic workup of a radiologic abnormality proceeds sequentially from sputum to bronchoalveolar cytology, and, if necessary, to fine-needle aspiration biopsy (FNA). Initial use of FNA in lung cancer diagnosis is controversial, but increasingly popular. We therefore decided to objectively assess current practice in cytologic lung cancer diagnosis at our institution. All pulmonary cytologic diagnoses for 1993 and the first half of 1994 were retrieved. Positive diagnoses were then used to access all patient data. Patients were stratified according to the specimen from which the first positive diagnosis was obtained. Of 542 pulmonary cytology specimens, 15% were sputa, 65% were bronchoalveolar, and 20% were FNAs. One hundred sixty-one of 172 malignant diagnoses were first diagnoses. Three percent of first malignant diagnoses were made from sputa, 47% were from lavages, and 50% were from FNAs. Although FNAs comprised just 20% of all pulmonary cytologies, 50% of all new malignant cytologic diagnoses were made by FNA. Initial use of FNA is successful, has a high diagnostic yield and low complication rate, and offers the most direct approach to diagnosis.

Biopsy, Needle↗
PubMed1996

Neuroendocrine differentiation in gastric adenocarcinomas. An immunohistochemical study.

BACKGROUND: The stomach contains a wide variety of neuroendocrine cells. Early studies with argyrophilic stains documented the presence of these cells in gastric adenocarcinomas. Immunohistochemical techniques for demonstrating hormones are more sensitive and specific and have been applied only sporadically to gastric adenocarcinomas. Thus, the true incidence of neuroendocrine cells in gastric adenocarcinomas is questionable. METHODS: Formalin-fixed, paraffin-embedded archival tissue specimens from 48 gastric adenocarcinomas were immunostained with antibodies to chromogranin A, synaptophysin, serotonin, gastrin, and neuron-specific enolase. The percentage of cells staining positively was evaluated semiquantitatively. RESULTS: Among 48 gastric adenocarcinomas, 36 (75%) stained positively for chromogranin A, 33 (69%) stained for synaptophysin, 29 (60%) stained for neuron-specific enolase, 17 (36%) stained for gastrin, and 15 (31%) stained for serotonin. The distribution of positivity was highest for chromogranin A (7 cases positive in 26% to 75% of cells) and lowest for serotonin (14 out of 15 cases stained in fewer than 1% of the cells present). CONCLUSIONS: Immunohistochemical evaluation of neuroendocrine markers in gastric adenocarcinomas indicates that a high percentage of tumors contain widely scattered single cells with neuroendocrine differentiation. Most often, however, such cells constitute only a small percentage of the total number of tumor cells present.

Adenocarcinoma↗
PubMed1995

Neuroanatomy of the external urethral sphincter: implications for urinary continence preservation during radical prostate surgery.

Post-prostatectomy urinary incontinence probably is multifactorial and sphincteric nerve injury could be a contributing cause. Controversy still exists regarding the innervation of the external sphincter, and currently pudendal nerve injury is not believed to be an etiological factor in post-prostatectomy urinary incontinence. To understand better the sphincter and its innervation, we undertook an anatomical and histological study of 18 adult male cadavers, which revealed that the external urethral sphincter receives part of its innervation through special branches originating from the dorsal nerve of the penis after it splits from the pudendal nerve. These nerve branches were located 0.3 to 1.3 cm. from the prostatic apex, and in 50% of the cadavers they were identified only unilaterally or had only 1 branch on each side. The proximity of these nerves to the prostatic apex may make them liable to injury during radical prostatectomy. These nerves are most likely sensory in nature although the presence of motor components cannot be completely ruled out. Injury to these nerves may explain several features of post-prostatectomy urinary incontinence.

Aged↗
PubMed1994

Ploidy status correlates with outcome in stage B prostate adenocarcinoma.

1. While there are extensive data showing that aneuploidy is associated with adverse outcome in stage D prostate cancer, the utility of ploidy analysis in stage B disease is unclear. We determined ploidy in radical prostatectomy specimens from 28 patients with clinical stage B prostate cancer, and with a mean follow-up of 4.1 years (2-10 years). Patients who had no recurrences had a minimum 5 years of follow-up. Patients who had only 2 years of follow-up were included if they had developed bone metastases during this period. 2. Ploidy determinations were done on Feulgen-stained 5-microns paraffin-embedded sections using a CAS 200 image analyzer. At least 400 tumor cells were counted in every case. Tumors with at least 70% diploid cells were classified as diploid, while those with less than 70% diploid cells were classified as aneuploid. The mean percentage of diploid cells in tumors classified as diploid was 90.6 +/- 7.4, while the mean percentage of diploid cells in tumors classified as aneuploid was 36 +/- 21.9. 3. Ploidy status correlated with disease progression: seven of the 10 patients (70%) with disease recurrence had aneuploid tumors, while 13 of 18 patients (72%) who remained disease-free had diploid tumors (P = 0.03, Chi-square test). 4. These data show that patients with stage B disease with aneuploid tumors at the time of prostatectomy are more likely to have recurrent disease within a mean of 3 years (2-6 years) compared to patients with diploid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

HLA expression by benign and malignant prostatic epithelium: augmentation by interferon-gamma.

Chronic prostatitis is a poorly understood entity that is characterized by lymphocytic infiltration of benign prostatic epithelium. Previously, we and others have shown that prostatic epithelium involved by prostatitis is phenotypically different from uninvolved epithelium. In addition, we have shown that malignant prostatic epithelium is rarely, if ever, infiltrated by lymphocytes. We now report that benign prostatic epithelium expresses HLA-DR only in the presence of lymphocytic inflammation, and that benign epithelium without chronic prostatitis and malignant prostatic epithelium do not express HLA-DR. In order to determine whether HLA-DR expression is inducible on malignant prostatic epithelium and therefore, at least theoretically, susceptible to immune regulation, we studied the DU-145 cell line in culture under various conditions. DU-145 cells did not express HLA-DR under routine culture conditions. However, the addition of interferon-gamma (100 to 6000 U/ml.) resulted in HLA-DR expression by DU-145 cells at 24 hours with maximal expression by 72 hours. In contrast, other cytokines (tumor necrosis factor, interleukin-1, interleukin-2) had no effect on HLA-DR expression. These investigations show that interferon-gamma induces HLA-DR expression on the DU-145 prostatic adenocarcinoma cell line, raising the theoretical possibility that malignant prostatic cells may be induced in vivo to express HLA-DR and thus become susceptible to immune regulation.

Adenocarcinoma↗
PubMed1993

Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma.

Tumor growth and metastasis require angiogenesis; and microvessel density, a measure of tumor angiogenesis, correlates with metastasis in breast and lung carcinoma. To determine how microvessel density correlated with metastasis in prostate carcinoma, we counted microvessels within the initial invasive carcinomas of 74 patients (29 with metastasis, 45 without). Microvessels were highlighted by immunostaining endothelial cells for factor VIII-related antigen. Without knowledge of the patient's cancer stage, microvessels were counted in a 200 field (0.739 mm2) in the most active areas of neovascularization. The mean microvessel count in tumors from patients with metastases was 76.8 microvessels per 200 field (median, 66; standard deviation, 44.6). The counts within carcinomas from patients without metastasis were significantly lower, 39.2 (median, 36; standard deviation, 18.6) (P < 0.0001). Microvessel counts increased with increasing Gleason's score (P < 0.0001), but this increase was present predominantly in the poorly differentiated tumors. Although Gleason's score also correlated with metastasis (P = 0.01), multivariate analysis showed that Gleason's score added no additional information to that provided by microvessel count alone. Assay of microvessel density within invasive tumors may prove valuable in selecting patients for aggressive adjuvant therapies in early prostate carcinoma.

Adult↗
PubMed1992

Correlation of Pneumocystis carinii cyst density with mortality in patients with acquired immunodeficiency syndrome and pneumocystis pneumonia.

Fifteen percent to 20% of patients with the acquired immunodeficiency syndrome and pneumocystis pneumonia do poorly despite early intervention. It is not known what distinguishes those who die, despite early intervention and aggressive therapy, from those who readily respond to therapy. We used image analysis to determine the relative abundance of cysts within aggregates of Pneumocystis carinii found in induced sputa (21 patients) and bronchoalveolar lavage fluid (14 patients) from 35 patients with pneumocystis pneumonia. We calculated a cyst density (number of cysts per area of aggregate) for each aggregate and a mean cyst density for all of the aggregates on the smear. Six patients died within 2 weeks of diagnosis; four of these six patients who had autopsies all had residual P carinii. The mean cyst density for those who died was 9.7 +/- 3.9 (range, 5 to 15 x 10(-3)). The 29 patients who survived beyond 2 weeks had a mean cyst density of 18.4 +/- 8.7 (range, 5 to 35 x 10(-3); P = .01). Mean cyst density was not influenced by the number of aggregates present in the smear, the variation in cyst density among aggregates in a smear, or the episode of pneumocystis pneumonia. Cyst density determinations alone should not be used to predict outcome for individuals with P carinii pneumonia until further study is completed. Nevertheless, the current study suggests that a low cyst density specimen, which may indirectly indicate a greater proportion of trophozoites compared with a high cyst density specimen, may be associated with an unfavorable outcome in acquired immunodeficiency syndrome-associated pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines.

Metastatic variants of human prostatic adenocarcinoma cell lines (DU-145, LNCaP, and ND-1) were studied by using soft agar colony forming efficiency, nude mice tumorigenicity, in vitro invasion assay, and type IV collagenase assay. The DU-145 and ND-1 cell line showed higher metastatic potential than LNCaP. Lipids from DU-145, ND-1, and LNCaP cells were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. The major lipids were phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, fatty acids, and cholesterol. The sphingomyelin level was significantly higher in highly metastatic cells (DU-145 and ND-1) compared with the lower metastatic variant (LNCaP). The increase in the synthetic pathway and decrease in degradation pathway of sphingomyelin in microsomal fractions was sufficient to account for the measured increase in sphingomyelin in DU-145 cells compared with LNCaP cells. The major fatty acids of these lipids were palmitic (16:0), stearic (18:0), oelic (18:1), and arachidonic acid (20:4). The arachidonic acid level was significantly decreased in DU-145 and ND-1 compared with LNCaP cells. Electron microscopic studies showed no significant changes in the morphology of DU-145, ND-1, and LNCaP cells. The results of these investigations demonstrate for the first time that sphingomyelin and arachidonic acid contents are different in high and low metastatic variants of human prostatic adenocarcinoma cell lines.

Adenocarcinoma↗
PubMed1992

Correlation of morphologic diagnosis of Pneumocystis carinii with the presence of pneumocystis DNA amplified by the polymerase chain reaction.

We compared the presence of P. carinii in clinical specimens as detected by standard cytomorphologic techniques with amplification of P. carinii-specific DNA by the polymerase chain reaction (PCR). Results correlated in 33 of 37 instances (89%): nine specimens were positive by both PCR and morphology; 24 specimens were negative by both techniques. Two specimens from one patient were obtained 3 days apart. The first specimen was both cytologically and PCR negative, while the second specimen was both cytologically and PCR positive for P. carinii. At least in some instances, therefore, PCR is no more sensitive than morphology, and other factors such as specimen adequacy are more important. Twelve of the 24 negative specimens were from patients with prior histories of P. carinii pneumonia, suggesting that recurrent disease may be from reacquisition of organisms in previously exposed individuals, rather than reactivation of latent organisms. Discrepant results included three morphologically negative specimens that were positive by PCR. It remains to be determined whether the increased sensitivity of PCR in these cases is real or artifactual. One morphologically positive specimen was negative by PCR. Polymerase chain reaction correlates well with cytomorphologic diagnosis of P. carinii pneumonia and may be a valuable diagnostic and epidemiologic tool.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Incidental lymphocytic prostatitis. Selective involvement with nonmalignant glands.

We documented the presence of lymphocytic prostatitis in all prostate specimens received over a 4-month period. Lymphocytic prostatitis was present in 44% of biopsy specimens (n = 77), 95% of transurethral prostatic resection specimens (n = 20), and 100% of total prostatectomy specimens (n = 9). The patchiness of the prostatitis within the prostate in part explains the lower prevalence in the biopsy specimens, which sample a much smaller portion of the gland compared with the other procedures. Lymphocytic prostatitis was seen in prostates both with and without adenocarcinoma. However, in specimens containing carcinoma, the lymphocytic aggregates rarely involved malignant glands. Instead, the aggregates were either stromal or involved nonmalignant glands either adjacent to or away from the tumor, including glands with hyperplasia, atrophy, and prostatic intraepithelial neoplasia. Even when malignant and nonmalignant glands were in close proximity, there was a sharp demarcation with respect to lymphocytic inflammation. Immunohistochemical staining with B-cell and T-cell markers disclosed that the vast majority are T lymphocytes. The localization of lymphoid aggregates to nonmalignant (including prostatic intraepithelial neoplasia) glands but not frankly neoplastic glands, suggests a selective escape of immune detection by neoplastic glands.

Adenocarcinoma↗
PubMed1992

Detection of antibodies to Pneumocystis carinii in bronchoalveolar lavage fluid by immunoreactivity to Pneumocystis carinii within alveoli, granulomas, and disseminated sites.

Although Pneumocystis carinii pneumonia (PCP) is the most common major opportunistic infection in the acquired immunodeficiency syndrome (AIDS), its immunopathogenesis is not fully understood. It is known that anti-pneumocystis antibodies are present in the sera of individuals with and without PCP. In order to determine whether anti-pneumocystis antibodies are also present in bronchoalveolar lavage fluid (BAL), we looked for them, by immunoreactivity with tissue sections of intra-alveolar P. carinii, in the BAL of (a) HIV-seropositive patients with PCP (n = 18); (b) HIV-seropositive patients without PCP (n = 11); and (c) HIV-seronegative patients with nonpneumocystis lung disease (n = 5). BALs from 19 of 29 HIV-seropositive patients were deficient in at least one isotype (13 with PCP, six without PCP), while only one of five HIV-seronegative patients was deficient. Despite the considerable documentation of atypical presentations of disease caused by P. carinii, little is known concerning the mechanisms involved. To determine whether there is any relationship between BAL anti-pneumocystis antibodies and diverse host responses, we studied antibody binding to P. carinii in different settings. IgG antibodies in BAL bound P. carinii within spleen, liver, skin, and muscle, as well as within pulmonary alveoli and granulomas. However, IgA antibodies in BAL bound intraalveolar and disseminated P. carinii but did not bind to P. carinii within pulmonary granulomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Fungal↗
PubMed1990

Localization of host immunoglobulin G to the surface of Pneumocystis carinii.

In immunoblotting studies of Pneumocystis carinii surface proteins, we found that a secondary antibody, anti-human immunoglobulin G (IgG), recognized a 52-kilodalton (kDa) band in homogenates of P. carinii purified from human autopsy lungs and bronchoalveolar lavage fluids, even when serum as a source of primary antibody was omitted. The electrophoretic mobility of the 52-kDa band is identical to that of IgG heavy chains. In addition to affinity-purified, anti-human IgG, monoclonal antibodies specific for the Fab and Fc regions of human IgG recognized the 52-kDa band. To determine whether the 52-kDa band represents IgG bound to the surface of P. carinii, we treated intact organisms with Triton X-100 and acid in order to elute immunoglobulin from the surface of P. carinii. After purification over a protein G column, the eluate comigrated with human IgG, was recognized by anti-IgG, and bound to discrete bands with molecular sizes of 65 to 70, 60, 50, and 35 kDa in purified, rat-derived P. carinii. To confirm the presence of human IgG on the surface of P. carinii, we performed immunocytochemical and immunoelectron microscopic studies. Staining of intact P. carinii aggregates by anti-human IgG was pronounced and was abolished by acid treatment. IgA was also present. Ultrastructural studies showed the presence of IgG on the cyst wall and on fine membranous structures and vesicles adjacent to cysts. We conclude that the surface of P. carinii is coated with human IgG. The close association of human IgG with P. carinii may have implications for the pathogenesis of P. carinii pneumonia in acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes.

Pulmonary infections with Pneumocystis carinii are an important cause of morbidity and mortality in patients with AIDS. P. carinii infections are seen in patients with decreased numbers of helper T lymphocytes, suggesting that these cells are important in preventing infection. To test this hypothesis, we sought to establish experimental infection with P. carinii in mice selectively depleted of helper T lymphocytes. Weekly injections of a monoclonal anti-CD4 antibody produced sustained depletion of helper T lymphocytes from blood and lymphoid organs. To establish pulmonary infection, lymphocyte-depleted mice were then given intratracheal inoculations of P. carinii organisms derived from the lungs of chronically infected athymic mice. Pulmonary infection with P. carinii was demonstrable in the antibody-treated mice and was centered around the conducting airways. Infection was persistent for up to 3 mo with continued antibody treatments, and yet could be cleared from the lungs if antibody treatments were discontinued. This experimental model of P. carinii infection permits the study of infection associated with a specific immune defect and implicates the helper T lymphocyte as a critical cell in host defense against this pathogen.

Animals↗
PubMed1989

In vitro differentiation of human-derived Pneumocystis carinii.

Two major impediments to the development of an in vitro cultivation system for Pneumocystis carinii are lack of an accurate means of quantitation and difficulty in determination of viability over time. Human-derived P. carinii exists as aggregates of cysts and trophozoites in bronchoalveolar lavage fluid. These aggregates persisted over time in an in vitro system consisting of a monolayer of radiated or nonradiated A549 cells, RPMI 1640, and 10% fetal calf serum. Parallel measurements at specified times after introduction into the in vitro system of the number of aggregates, total aggregate area, and total number of cysts varied and appeared to be a function of the number of aggregates initially added into the system. However, cyst density, the number of cysts per unit aggregate area, was independent of the total number of aggregates added into the system. Cyst density was determined by staining an aggregate with a cyst-specific stain, such as toluidine blue, and counterstaining with Diff-Quik, allowing simultaneous visualization of cysts and aggregate area. Preliminary experiments suggested an increase in cyst density over time. Cyst density may be a means of accurate in vitro quantitation of P. carinii.

Acquired Immunodeficiency Syndrome↗