Neuroendocrine carcinomas (carcinoid tumor) of the testis. A clinicopathologic and immunohistochemical study of ten cases

We studied 10 cases of primary pure testicular neuroendocrine carcinoma. Patients were between 16 and 48 years old and had testicular swelling with pain or a painless testicular mass and no history of neuroendocrine carcinoma or other malignant neoplasm. All underwent orchiectomy. The tumors were low (n = 9) and intermediate (n = 1) grades with a variegated histologic appearance characterized by a nesting pattern, cords of neoplastic cells with rosettes, or sheets of neoplastic cells. Mitotic activity was lacking in 9 cases. In 1 case, mitotic figures ranged from 7 to 8 per 10 high-power fields, and cellular atypia and comedo-like necrosis were present. Immunohistochemical studies using a keratin cocktail, chromogranin, synaptophysin, epidermal growth factor, p53, placental-like alkaline phosphatase, and CD117 (c-kit) were performed in all cases. Keratin, chromogranin, and synaptophysin were positive in all tumors. Clinical follow-up information was obtained for 6 patients (range, 12-60 months): 5 with low-grade tumors were alive 24 to 60 months after diagnosis; 1 with an intermediate-grade tumor died of tumor 12 months after initial diagnosis. The behavior of these tumors, while in the testicular region, correlates well with the histologic grade. We propose replacing the term testicular carcinoid with neuroendocrine carcinoma, which better reflects the nature of these neoplasms.     

Evaluations of commercial West Nile virus immunoglobulin G (IgG) and IgM enzyme immunoassays show the value of continuous validation

West Nile virus was introduced into the United States in 1999 and in only four seasons has become endemic east of the Rocky Mountains. Recently, immunoglobulin M (IgM)-capture enzyme immunoassays for the detection of West Nile virus-specific IgM and indirect IgG enzyme immunoassays for the detection of IgG antibodies against West Nile virus were made available from Focus Technologies and PANBIO, Inc. We evaluated these commercial IgG and IgM test systems and determined agreement, sensitivity, and specificity for the assays, compared to immunofluorescence assay and the Centers for Disease Control and Prevention's IgM-capture enzyme-linked immunosorbent assay (ELISA). Initially, the Focus and PANBIO IgM enzyme immunoassays had at least 95% agreement, sensitivity, and specificity, and, based on the 95% confidence intervals, both IgM-capture assays performed similarly. The IgG assays also performed well, although the Focus IgG assay demonstrated greater specificity (98.8%) and the PANBIO IgG assay demonstrated greater sensitivity (99.3%). However, for 400 samples consecutively submitted for West Nile virus antibody testing during 2 days of the 2003 West Nile virus season, agreement, clinical sensitivity, and clinical specificity were 93.1, 98.0, and 92.4%, respectively, for the PANBIO IgM assay and were 97.4, 100.0, and 97.1%, respectively, for the Focus IgM assay. The specificities observed in this second evaluation equates to an overall false-positivity rate of 6.3% in the PANBIO West Nile virus IgM-capture ELISA versus 2.5% with the Focus West Nile virus IgM-capture ELISA. This experience demonstrates the importance of continuously evaluating the performance of an assay in order to detect any changes in assay performance as the test population evolves.     

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

Background  

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process.     

The Helix aspersa (brown garden snail) allergen repertoire

BACKGROUND: Ingestion of snails can induce strong asthmatic or anaphylactic responses, mainly in house-dust-mite-sensitized patients. The aim of this study was to identify the Helix aspersa (Hel a), Theba pisana (The p) and Otala lactea (Ota l) allergens and the extent of their cross-reactivity with the Dermatophagoides pteronyssinus (Der p) mite. PATIENTS AND METHODS: In 60 atopic patients, skin prick tests (SPT) to snail and D. pteronyssinus, total and specific IgE, specific IgE immunoblots, RAST and immunoblot inhibition assays were performed. RESULTS: Mean total IgE was >1,000 kU/l. Mean specific IgE (class 6 for Der p and class 2 for Hel a) SPT were positive in 44 patients for snail and in 56 for mite. Isoelectric focusing (IEF) and SDS-PAGE followed by immunoblotting of H. aspersa extract enabled the identification of 27 and 20 allergens, respectively. Myosin heavy chains from snails (molecular weight >208 kDa) disclosed two major allergens. Hel a and Der p RAST were strongly inhibited by their homologous extracts, with Hel a RAST being inhibited by the Der p extract to a much greater extent (72.6%) than the inverse (5.6%). A complete inhibition of the immunoblots by their homologous extract was obtained. However, Hel a extract did not inhibit Der p IEF separated recognition. On the other hand, mite extract extensively inhibited snail immunoblots from both IEF and SDS-PAGE separations. Immune detection on chicken, pig, rabbit, cow and horse myosins did not reveal any IgE cross recognition with snail. CONCLUSIONS: In most cases of snail allergy, mite appeared to be the sensitizing agent. Nevertheless, snails may also be able to induce sensitization by themselves. This hypothesis is supported by the finding of specific IgE to Hel a in 2 patients who did not show specific IgE to Der p, and one of them was suffering from asthma after snail ingestion.     

Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse

In humans, maternal fibrinogen (Fg) is required to support pregnancies by maintaining hemostatic balance and stabilizing uteroplacental attachment at the fibrinoid layer found at the fetal-maternal junction. To examine relationships between low Fg levels and early fetal loss, a genetic model of afibrinogenemia was developed. Pregnant mice homozygous for a deletion of the Fg-gamma chain, which results in a total Fg deficiency state (FG(-/-)), aborted the fetuses at the equivalent gestational stage seen in humans. Results obtained from timed matings of FG(-/-) mice showed that vaginal bleeding was initiated as early as embryonic day (E)6 to 7, a critical stage for maternal-fetal vascular development. The condition of afibrinogenemia retarded embryo-placental development, and consistently led to abortion and maternal death at E9.75. Lack of Fg did not alter the extent or distribution pattern of other putative factors of embryo-placental attachment, including laminin, fibronectin, and Factor XIII, indicating that the presence of fibrin(ogen) is required to confer sufficient stability at the placental-decidual interface. The results of these studies demonstrate that maternal Fg plays a critical role in maintenance of pregnancy in mice, both by supporting proper development of fetal-maternal vascular communication and stabilization of embryo implantation.     

Hepatitis B virus transmission in Brazilian hemodialysis units: serological and molecular follow-up

A serological and molecular study of hepatitis B virus (HBV) infection was carried out in dialysis units in Central Brazil. Between 1995 and 1999, serum samples from all HBsAg-positive hemodialysis patients (n = 43) were tested for HBeAg/anti-HBe and subtyping by monoclonal ELISA. HBV DNA was detected by PCR and positive samples were genotyped by restriction fragment polymorphism pattern (RFLP) methodology. TheHBsAg prevalence declined in this population during the survey period (12-5.8%). HBeAg and anti-HBe were detected in 23 (53.5%) and 18 (41.9%) sera, respectively. Thirty-six samples could be HBsAg subtyped: 21 were subtype ayw(3), 14 belonged to adw(2) and one was identified as adw(4). HBV DNA was present in 30 serum samples. Of these, 20 (66.7%) were genotype D, 9 (30%) genotype A, and 1 (3.3%) genotype F. In addition, the RFLP pattern could be determined in samples from 18/20 genotype D patients: D3 (10 strains), D7 (7 strains) and D4 (1 strain); from 8/9 genotype A patients: A1 (6 strains) and A3 (2 strains); and from the patient infected with genotype F: F1. Patterns D3 and D7 were associated closely with HBV infection in the two largest hemodialysis units studied. These findings confirm the value of the RFLP method as an effective molecular epidemiological tool for elucidating HBV transmission in hemodialysis units.     

Cervical cancer screening program of Paraná: cytohistological correlation results after five years

Since its inception in November 1997, the Cervical Cancer Screening Program of Paraná (CCSPP), Brazil, has resulted in the cytological screening of 2,244,158 women, the coverage of the female population increasing from 43% to 86%. One thousand six hundred one cases screened by cytology, submitted to colposcopy, and subjected to treatment were selected. Cytopathological results were compared with those obtained on the basis of histological analyses of the loop electrical excision procedure specimens, and were subjected to statistical analyses. The data obtained were then compared with cytohistological correlation results from the first year of the program. Considering the exact correlation between cytological and histological diagnoses, the correlation index increased from 53.34% in the first year to 67.3% at the end of 5 yr of the program. Variations that occurred in each diagnostic category are discussed. This study demonstrates a significant improvement in the concordance between cytological and histological results for the 5-yr period compared with the first year of the CCSPP.     

Personality, manual preference and neuroendocrine reactivity in hirsute subjects

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.     

Effects of novel manufacturing technology on blood and dialysate flow distribution in a new low flux "alpha Polysulfone" hemodialyzer

The main target for low flux hemodialyzers is an efficient low molecular weight solutes clearance. Such efficiency is largely dependent on the optimization of diffusion between blood and dialysis solution. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. Thus optimized flow distribution both in the blood and dialysate compartment becomes quintessential for the maximal efficiency of the diffusion process within the hemodialyzer. The present paper describes the distribution of the blood and dialysate flows in a new low flux polysulfone hollow fiber hemodialyzer characterized by a specific undulation of the fibers and a new cutting technology of the fibers for an improved micro-flow condition in the blood compartment headers. Twelve Diacap alpha Polysulfone LO PS 15 (1.5 sqm) (B.Braun Medizintechnologie, Melsungen Germany) were employed for the study. Six were analyzed in vitro and six were studied in vivo. Blood flow distribution was studied in vitro by dye injection in the blood compartment during experimental extracorporeal circulation utilizing human blood with hematocrit adjusted at 33%. Sequential images were obtained with a helical scanner in a fixed longitudinal section of the dialyzer 1 cm thick. Average and regional blood flow velocities were measured utilizing the reconstructed imaging sequence. The method allowed the calculation of single fiber blood flow (SF Qb) and the mass transfer zone (MTR) definition in digitally subtracted images. The patterns 20-10 and 40-30 were utilized. The same technology was used to evaluate flow distribution in the dialysate compartment after dye injection in the Hansen's connector. Regional dialysate flow was calculated in central and peripheral sample areas of 1 cm2. Six in vivo hemodialysis treatments on patients with end stage renal disease were performed at three different blood flow rates (250-350 and 450 ml/min) in order to measure urea, creatinine and phosphate clearance. Macroscopic and densitometrical analysis revealed that flow distribution was homogeneous in the blood compartment while in the dialysate compartment a slight difference between the peripheral and central regions in terms of flow velocity was observed. This however was not generating channeling phenomena. Urea creatinine and phosphate clearances were remarkably high and so were the Kt/V observed in all sessions, especially in relation to the studied blood flows. In conclusion, a significant blood to dialysate flow match with optimized countercurrent flow condition was observed in the studied hollow fiber hemodialyzers. Such optimization might be due both to the improved dialyzer design at the level of the blood header and to the specific fiber undulation that prevents dialysate channeling.