A liquid-scintillation-based primary standardization of Pb

A new radioactivity solution standard of ²¹⁰Pb has been developed and will be disseminated by the National Institute of Standards and Technology (NIST) as standard reference material (SRM) 4337. This new ²¹⁰Pb solution standard is contained in a 5 mL flame-sealed borosilicate glass ampoule, consists of (5.133±0.002) g of a nominal 1 mol L⁻¹ nitric acid solution, has a density of (1.028±0.002) g mL⁻¹ at 20 °C, has carrier ion concentrations of about 11 μg Pb²⁺ and 21 μg Bi³⁺ per gram of solution, and is certified to contain a massic activity (9.037±0.22) kBq g⁻¹ as of the reference time 1200 EST, 15 June 2006. All of the uncertainties cited above correspond to standard uncertainties multiplied by a coverage factor k=2. The standardization for the ²¹⁰Pb content of the solution was based on 4πβ liquid scintillation (LS) measurements using CIEMAT/NIST ³H-standard efficiency tracing (CNET). Confirmatory determinations were also performed by high-resolution HPGe γ-ray spectrometry, by 2π spectrometry with a Si surface barrier detector of separated ²¹⁰Po, and by 4πβ(LS)–γ(NaI) anticoincidence counting.     

A note on the half-life of 209Po.

The widely adopted value of (102+/-5)a for the (209)Po half-life, which is based on a single determination reported in 1956, appears to be in error by a large factor. Decay data from two separate primary standardizations of a (209)Po solution standard, conducted approximately 12 years apart, are inconsistent with the adopted value and its assigned uncertainty. An estimated half-life, larger than the adopted value by about 25%, is more consistent with the standardization data. A longer half-life is also supported by measurements on a recently standardized (210)Pb solution standard.     

Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.     

Immunohistochemistry (S 100, KL 1) and human papillomavirus DNA hybridization on Morbus Bowen and bowenoid papulosis

Summary In this study 55 paraffin embedded samples defined as Bowen's disease or bowenoid papulosis were investigated with antibodies against S 100 protein and keratins (KL 1). S 100-positive cells were quantified and related to defined section area of the epidermal compartment by computer-assisted image analysis. The density of S 100-positive cells was compared with normal skin and was particularly related to growth patterns and keratinization of the different lesions under study. S 100-positive dendritic cells were found to be reduced overall in bowenoid lesions when compared with normal skin. Lesions with high counts of S 100-positive dendritic cells most frequentty showed a solitary growth pattern with highly conserved architecture and differentiation and no tendency to stromal invasion. In contrast, cases with low counts of S 100-positive cells very often showed multifocal development, a high degree of architectural disturbance and dedifferentiation. In this group, stromal invasion (cases of invasive carcinoma associated with Bowen's disease) was seen more often. Interestingly, this latter group of cases also revealed a peculiar keratin pattern. Frequently, the basal cell layer was decorated with KL 1 antibody, which usually recognizes only suprabasaly located keratinocytes. No differences between Bowen's disease and bowenoid papulosis were found in terms of densities of S 100-positive dendritic cells and keratin pattern. In our experience, extragenital Bowen's disease and genital Bowen's disease can not be distinguished on purely morphological grounds or with the immunocytochemical approach presented here. Interestingly, when employing in situ hybridization with HPV 16 probes three of seven samples of genital Bowen's disease harboured HPV 16 DNA, whereas six cases of extragenital disease were negative.Supported by the Deutsche Forschungsgemeinschaft (Lo 285/2-4)     

Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.     

Moderne immuntherapeutische Ansätze für die Behandlung von Lungen- und Kopf-Hals-Tumoren

Zusammenfassung Multimodale Therapiestrategien, die Chirurgie, Strahlen- und Chemotherapie kombinieren, haben die Behandlungsergebnisse bei Tumoren der Lunge und der Kopf-Hals Region verbessert. Die Ergänzung des Therapiespektrums um weitere Ansätze, die sich in der Wirkungsweise und möglichst durch reduzierte Toxizität von den konventionellen unterscheiden, erscheint jedoch zur Erzielung weiterer Fortschritte notwendig. Eine neue Generation immunologischer passiver (antikörperbasierter) und auch aktiver (Vakzinierungs-) Strategien erscheint aussichtsreich und befindet sich gegenwärtig in der klinischen Prüfung. Die Untersuchung der optimalen zeitlichen Sequenz in Kombination mit den konventionellen Therapieverfahren und die Individualisierung der Therapie auf Basis genomischer/proteomischer Daten muss die klinische Integration begleiten.     

Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity

BACKGROUND: Xenogeneic DNA immunization can exploit small differences in expressed protein sequence resulting in immune recognition of self-molecules. We hypothesized that immunizing mice with xenogeneic DNA coding for the human melanosomal membrane glycoprotein gp100 would overcome immune ignorance or tolerance and result in tumor immunity. We also investigated the immunologic mechanisms of the antitumor immunity. METHODS: C57BL/6 mice were immunized with DNA coding for human gp100, mouse gp100, or control vector by gene gun. After immunization, mice were challenged with a syngeneic melanoma expressing gp100, and tumor growth was analyzed. Mice deficient in major histocompatibility complex class I or class II molecules were similarly studied to assess the immunologic mechanism of the tumor protection. RESULTS: There was significant tumor protection after vaccination with xenogeneic human gp100 DNA. Class I, but not class II, major histocompatibility complex molecules were required for tumor immunity. In addition, mice immunized with human gp100 demonstrated autoimmunity manifested as coat color depigmentation. CONCLUSIONS: Immunization with xenogeneic DNA coding for the melanosomal glycoprotein gp100 results in tumor protection and autoimmune depigmentation. These results show that xenogeneic DNA vaccines can lead to cancer immunity without CD4(+) T-cell help with potential implications for rational vaccine design.     

Peritoneal and intestinal tuberculosis: an ancestral disease that poses new challenges in the technological era. Case report and review of the literature

Tuberculosis is a public health problem. The most common presentation is pulmonary disease. The diagnosis of any extrapulmonary forms are quite difficult. Clinical manifestations of gastrointestinal tuberculosis are non-specific and compatible with pathologies such as inflammatory bowel disease, advanced ovarian cancer, deep mycosis, yersinia infection and amebomas. Abdominal form is located at 6th place of the extrapulmonary forms, after lymphatic, genitourinary, osteoarticular, miliary and meningeal infections. Eventually, 25 to 75% of patients with abdominal tuberculosis will require surgery. These procedures should be limitated with the purpose to preserve small bowel. Resection should be limitated for complicated cases. The surgical indications include: Intestinal occlusion (15-60%), perforation (1-15%), abscesses and fistulas (2-30%) and hemorrhage (2%). CONCLUSIONS: In most of the cases, the diagnosis of peritoneal or intestinal tuberculosis is made during a laparoscopy or laparotomy even during surgery performed by different purposes. Excessive manipulation of the intraabdominal organs may produced unexpected bowel lesions, increasing morbidity and mortality. Medical treatment is highly effective in the resolution of moderate complications such as bowel obstruction. Resectional procedures should be reserved for complications like perforation, bleeding or stenosis non-suitable for stricturoplasty.     

Elevation in serum thyroglobulin during prolonged Antarctic residence: effect of thyroxine supplement in the polar 3,5,3'-triiodothyronine syndrome

Extended Antarctic residence (AR) is associated with an increase in serum TSH, a decrease in free T(4), and an increase in T(3) production and clearance. It is not clear whether these adaptations reflect changes in clearance alone or whether intrinsic thyroidal synthetic activity also changes. Thyroglobulin (Tg) secretion is an independent marker of intrinsic thyroid activity whose kinetics are independent of those of T(3) and T(4). In this study we examined changes in Tg levels in healthy subjects before and during AR and their responses to thyroid supplementation to help determine whether alterations in thyroid activity, and not just kinetics of clearance, underlie the changes seen with the polar T(3) syndrome. In cohort 1, we compared measurements of TSH and Tg in 12 subjects before deployment and monthly for 11 months during AR. In cohort 2, we compared the same measurements in 12 subjects monthly for 11 months of AR. Subjects were randomized to receive either placebo or levothyroxine in cohort 1 for 7 months and in cohort 2 for 11 months. Tg increased over baseline during the first 4 months of AR by 17.0 +/- 4.6% and after 7 more months by 31.7 +/- 4.3% over baseline in the placebo group of both cohorts (P < 0.0002). When L-T(4) was taken, Tg returned to a value not different from baseline (4.5 +/- 3.9%). The percent changes from baseline in serum TSH and Tg during AR were highly correlated (P < 0.00003) in the placebo group for both cohorts. The rise in Tg with TSH and the reduction in Tg with L-T(4) provide evidence of target tissue response to TSH and further confirm the TSH rise as physiologically significant. The results also suggest that the adaptive changes in thyroid hormone economy with AR reflect TSH-dependent changes in thyroid synthetic activity, which may help explain a portion of the increases in T(3) production found with AR.