Successful selective internal radiotherapy (SIRT) in a patient with a malignant solid pseudopapillary pancreatic neoplasm (SPN).

Solid pseudopapillary neoplasms of the pancreas (SPNs, Gruber-Frantz-Tumor) are a rare entity representing 1-5% of all exocrine pancreatic tumors. The pseudocystic lesions preferentially affect young females <30 years, are mostly benign (∼90%) and normally present with unspecific symptoms. We describe the case of a 16-years-old Asian woman that was initially diagnosed with an SPN in the pancreatic head with mesenterial and hepatic metastases. After diagnosis, an extensive tumor resection was performed including pyloric-preserving pancreatic head resection followed by sequential resection of all hepatic metastases. After the patient was diagnosed with a hepatic recurrence and high intrahepatic tumor load, we chose a multimodal procedure and performed a selective internal radiotherapy (SIRT). Four years after SIRT and 10 years after initial diagnosis of metastatic SPN, the patient is in a good condition without any evidence for hepatic recurrence. This case represents a rare clinical course of a malignant and invasive SPN with an exceptionally long survival despite of high initial tumor burden. The selective internal radiotherapy is a suitable approach for inducing long-term remissions of the strongly vascularized liver metastases.

Biologically based strategies to augment rotator cuff tears.

Lesions of the rotator cuff (RC) are among the most frequent tendon injuries. In spite of the developments in both open and arthroscopic surgery, RC repair still very often fails. In order to reduce the failure rate after surgery, several experimental in vitro and in vivo therapy methods have been developed for biological improvement of the reinsertion. This article provides an overview of the current evidence for augmentation of RC reconstruction with growth factors. Furthermore, potential future therapeutic approaches are discussed. We performed a comprehensive search of the PubMed database using various combinations of the keywords "tendon," "rotator cuff," "augmentation," "growth factor," "platelet-rich fibrin," and "platelet-rich plasma" for publications up to 2011. Given the linguistic capabilities of the research team, we considered publications in English, German, French, and Spanish. We excluded literature reviews, case reports, and letters to the editor.

Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat.

Exposure to intrauterine growth restriction (IUGR) is an important risk factor for impaired learning and memory, particularly in males. Although the basis of IUGR-associated learning and memory dysfunction is unknown, potential molecular participants may be insulin-like growth factor 1 (Igf1) and its receptor, IGF1r. We hypothesized that transcript levels and protein abundance of Igf1 and IGF1r in the hippocampus, a brain region critical for learning and memory, would be lower in IUGR male rats than in age-matched male controls at birth (postnatal day 0, P0), at weaning (P21) and adulthood (P120). We also hypothesized that changes in messenger Ribonucleic acid (mRNA) transcript levels and protein abundance would be associated with specific histone marks in IUGR male rats. Lastly, we hypothesized that IUGR male rats would perform poorer on tests of hippocampal function at P120. IUGR was induced by bilateral ligation of the uterine arteries in pregnant dams at embryonic day 19 (term is 21 days). Hippocampal Igf1 mRNA transcript levels and protein abundance were unchanged in IUGR male rats at P0, P21 or P120. At P0 and P120, IGF1r expression was increased in IUGR male rats. At P21, IGF1r expression was decreased in IUGR male rats. Increased IGF1r expression was associated with more histone 3 lysine 4 dimethylation (H3K4Me2) in the promoter region. In addition, IUGR male rats performed poorer on intermediate-term spatial working memory testing at P120. We speculate that altered IGF1r expression in the hippocampus of IUGR male rats may play a role in learning and memory dysfunction later in life.

Critical consideration of precipitate analysis of Fe-1 at.% Cu using atom probe and small-angle neutron scattering.

An Fe-1 at.% Cu model alloy was examined by atom probe (3DAP) and small-angle neutron scattering (SANS) to verify the accordance of the gained results. The Fe-Cu alloy was heat-treated for various times at 500°C, forming Cu-rich precipitates within the Fe matrix. The chemical compositions of the precipitates and matrix found by 3DAP were used to calculate the magnetic scattering contrast. Additionally, a magnetic moment of the precipitates that contain a significant amount of Fe was taken into account for the calculation of magnetic scattering contrast. This in turn is used for the evaluation of the magnetic scattering curves gained by SANS. Both the 3DAP data as well as the scattering curves were analyzed with regard to radius, number density, and volume fraction of the precipitates as a function of aging time. The results yielded by both techniques are in good agreement and correspond to the development of the hardness of the alloy. Minor differences can be related to the cluster search algorithm used for the analysis of the 3DAP data as well as Fe overestimation based on different field phases.

Precipitation evolution in a Ti-free and Ti-containing stainless maraging steel.

Stainless maraging steels have a Cr content higher than 12wt% and show a excellent combination of high strength and ductility, which make them attractive for use in machinery fields and aircraft applications. The massive increase of strength during ageing treatment of maraging steels is related to a precipitation sequence of various nm-scaled intermetallic phases. The peak hardness especially in Ti-containing maraging steels can be reached after short-time ageing at temperatures around 500 degrees C. However, precipitation reactions in different stainless maraging steels are not fully understood, especially the evolution from clustering over growing to coarsening. In the present work a commercial maraging steel and a Ti-containing model alloy are investigated and compared to each other. The steels were isothermally heat treated at 525 degrees C for a range of times. Special emphasis was laid on the correlation of hardness to the formation and presence of different kinds of precipitates. The isothermal aged samples were investigated by using two advanced three-dimensional energy compensated atom probes (LEAP and 3DAP) both in voltage mode and in laser mode. The atom probe data were correlated to standard hardness measurements. The results show that the partial substitution of Al by Ti results in a different precipitation behaviour. While the Ti-free maraging steel exhibit only one type of precipitate, the Ti-containing grade shows a change in the type of precipitates during ageing. However, this change leads to an accelerated coarsening and thus to a faster drop in hardness.

Identification of androgen-regulated genes in the prostate cancer cell line LNCaP by serial analysis of gene expression and proteomic analysis.

A common therapy for nonorgan-confined prostate cancer involves androgen deprivation. To develop a better understanding of the effect of androgen on prostatic cells, we have analyzed gene expression changes induced by dihydrotestosterone (DHT) in the androgen responsive prostate cancer line LNCaP, at both RNA and protein levels. Changes at the RNA level induced by DHT were determined by means of serial analysis of gene expression (SAGE), and protein profiling was done by means of quantitative two-dimensional polyacrylamide gel electrophoresis. Among 123,371 transcripts analyzed, a total of 28,844 distinct SAGE tags were identified representing 16,570 genes. Some 351 genes were significantly affected by DHT treatment at the RNA level (p < 0.05), of which 147 were induced and 204 repressed by androgen. In two independent experiments, the integrated intensity of 32 protein spots increased and 12 decreased at least two-fold in response to androgen, out of a total of 1031 protein spots analyzed. The change in intensity for most of the affected proteins identified could not be predicted based on the level of their corresponding RNA. Our study provides a global assessment of genes regulated by DHT and suggests a need for profiling at both RNA and protein levels for a comprehensive evaluation of patterns of gene expression.

Disfluency rates in conversation: effects of age, relationship, topic, role, and gender.

After reviewing situational and demographic factors that have been argued to affect speakers' disfluency rates, we examined disfluency rates in a corpus of task-oriented conversations (Schober & Carstensen, 2001 ) with variables that might affect fluency rates. These factors included: speakers' ages (young, middle-aged, and older), task roles (director vs. matcher in a referential communication task), difficulty of topic domain (abstract geometric figures vs. photographs of children), relationships between speakers (married vs. strangers), and gender (each pair consisted of a man and a woman). Older speakers produced only slightly higher disfluency rates than young and middle-aged speakers. Overall, disfluency rates were higher both when speakers acted as directors and when they discussed abstract figures, confirming that disfluencies are associated with an increase in planning difficulty. However, fillers (such as uh) were distributed somewhat differently than repeats or restarts, supporting the idea that fillers may be a resource for or a consequence of interpersonal coordination.

Mixed epithelial and stromal tumor of the kidney lacks the genetic alterations of cellular congenital mesoblastic nephroma.

Mixed epithelial and stromal tumor of the kidney is a recently recognized neoplasm that occurs almost exclusively in perimenopausal women. Because it frequently contains areas of smooth muscle in which epithelial structures are embedded, some have concluded that it is the adult form of congenital mesoblastic nephroma. Others have concluded that the morphology and epidemiology of mixed epithelial and stromal tumor indicate that it is unrelated to congenital mesoblastic nephroma. Although the genetic alterations of mixed epithelial and stromal tumor have not been previously elucidated, much is known about the genetic alterations of cellular congenital mesoblastic nephroma. The present study was undertaken to determine if mixed epithelial and stromal tumors have any of the genetic alterations recognized as typical of cellular congenital mesoblastic nephroma. RNA extraction was performed on formalin-fixed, paraffin-embedded tissue from 7 mixed epithelial and stromal tumors followed by reverse-transcription polymerase chain reaction to detect the ETV6-NTRK3 gene fusion. Fluorescent in situ hybridization with centromere-specific probes for chromosomes 8, 11, and 17 was performed to evaluate polyploidy of these chromosomes in 11 cases of mixed epithelial and stromal tumor. None of the mixed epithelial and stromal tumors showed any of these genetic alterations. We conclude that mixed epithelial and stromal tumor of the kidney lacks the genetic alterations typical of cellular congenital mesoblastic nephroma, is unrelated to it, and the appellation "adult mesoblastic nephroma" should not be used for these tumors.

Identification of differentially expressed genes by serial analysis of gene expression in human prostate cancer.

Prostate cancer is the leading cause of cancer death in American males. To better understand the genetic bases of this disease, we have generated a comprehensive molecular profile of human prostate. The gene expression pattern in normal and prostate cancer tissues was analyzed by serial analysis of gene expression (SAGE). A total of 133,217 transcripts were analyzed, and 35,185 distinct SAGE tags were identified representing 19,287 genes. Comparison of the transcripts in normal and tumor tissue revealed 156 differentially expressed genes (P < 0.05), of which 88 genes were up-regulated and 68 genes were down-regulated in the tumor tissue. Based on SAGE data, we estimate that the transcriptome for human prostate is approximately 37,000. Several differentially expressed genes identified by SAGE were selected for confirmation using immunohistochemistry. Some genes (e.g., E2F4) were overexpressed in tumor epithelial cells and some (e.g., Daxx) were increased in tumor stroma. Further characterization of the role of E2F4 and Daxx as well as other differentially expressed genes may provide useful insights into the mechanism of prostate cancer development.

Discovering resources--making global connections, international networking.

PURPOSE: To describe the key objectives, aims, activities and vision for the International Nurse Practitioner/Advanced Practice Nursing Network (INP/PNN). DATA SOURCES: Selected publications and documents, personal experience, and commentary. CONCLUSIONS: Advanced practice nursing and NP roles are prevalent in the United States and are now emerging in numerous countries throughout the world. There is a heightened interest among APNs and NPs internationally to share knowledge, expertise, and resources to enhance the presence of nursing in primary healthcare worldwide. The INP/APNN proposes to be an option for supporting the diversity of international networking in this field. IMPLICATIONS FOR PRACTICE: Nurse practitioner and APN roles are emerging globally. Globalization and global health issues impact all health care practitioners. Collaboration, partnering, and networking have the potential of enhancing and advancing practice for both experienced practitioners and countries that are initiating APN roles.

Molecular profiling in prostate cancer.

Prostate cancer is the most diagnosed cancer and the second leading cause of cancer death among men in the United States. Ability to detect this cancer early and availability of better prognostic markers are critical in order to decrease morbidity and mortality of prostate cancer. With the recent development in gene expression analysis methodology, expression profiles of thousands of genes can be generated in tissue samples and cell lines. Comparison of the global gene expression patterns between normal prostate and tumors at different stages may allow us to understand better the molecular mechanism of prostate tumorigenesis and progression. Different cancer cell lines and tissues appear to have different gene expression patterns that provide a new tool to classify tumors. Molecular classification of prostate cancer holds great promise for early detection and prognosis of this disease in the future. In this review, we summarize some of the recent mRNA and protein expression profiling studies performed in prostate cancer. Further, we discuss the potential benefits and limitations of current profiling technology.

Clarifying question meaning in a household telephone survey.

This study contrasts two interviewing techniques that reflect different tacit assumptions about communication. In one, strictly standardized interviewing, interviewers leave the interpretation of questions up to respondents. In the other, conversational interviewing, interviewers say whatever it takes to make sure that questions are interpreted uniformly and as intended. Respondents from a national sample were interviewed twice. Each time they were asked the same factual questions from ongoing government surveys, five about housing and five about recent purchases. The first interview was strictly standardized; the second was standardized for half the respondents and conversational for the others. Respondents in a second conversational interview answered differently than in the first interview more often, and for reasons that conformed more closely to official definitions, than respondents in a second standardized interview. This suggests that conversational interviewing improved comprehension, although it also lengthened interviews. We conclude that respondents in a national sample may misinterpret certain questions frequently enough to compromise data quality and that such misunderstandings cannot easily be eliminated by pretesting and rewording questions alone. More standardized comprehension may require less standardized interviewer behavior.

Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts.

Asymmetric cell divisions can be generated by the segregation of determinants into one of the two daughter cells. In Drosophila, neuroblasts divide asymmetrically along the apical-basal axis shortly after their delamination from the neuroectodermal epithelium. Several proteins, including Numb and Miranda, segregate into the basal daughter cell and are needed for the determination of its correct cell fate. Both the apical-basal orientation of the mitotic spindle and the localization of Numb and Miranda to the basal cell cortex are directed by Inscuteable, a protein that localizes to the apical cell cortex before and during neuroblast mitosis. Here we show that the apical localizaton of Inscuteable requires Bazooka, a protein containing a PDZ domain that is essential for apical-basal polarity in epithelial cells. Bazooka localizes with Inscuteable in neuroblasts and binds to the Inscuteable localization domain in vitro and in vivo. In embryos lacking both maternal and zygotic bazooka function, Inscuteable no longer localizes asymmetrically in neuroblasts and is instead uniformly distributed in the cytoplasm. Mitotic spindles in neuroblasts are misoriented in these embryos, and the proteins Numb and Miranda fail to localize asymmetrically in metaphase. Our results suggest that direct binding to Bazooka mediates the asymmetric localization of Inscuteable and connects the asymmetric division of neuroblasts to the axis of epithelial apical-basal polarity.

Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation.

High plasma concentrations of lipoprotein[a] (Lp[a]) are considered a genetically determined risk factor for atherosclerosis. Lp[a] is produced by the liver. The site(s) and mechanism(s) of catabolism are presently unclear. Lp[a] is elevated secondary to end-stage renal disease which suggests a direct or indirect role of the kidney in the metabolism of Lp[a]. We therefore investigated, by a simple in vivo approach, whether Lp[a] is removed by the human kidney. Lp[a] plasma concentrations were measured simultaneously by various methods in the ascending aorta and renal vein of 100 patients undergoing coronary angiography or coronary angioplasty. Lp[a] levels differed significantly between the two vessels even after correcting for hemoconcentration (20.1 +/- 21.6 mg/dL versus 18.7 +/- 20.3 mg/dL, P < 0.001). This corresponds to a mean arteriovenous difference of -1.4 mg/ dL or -9% of the arterial concentration. No Lp[a] or intact apo[a] could be detected in urine from healthy probands. Although we cannot assign the kidney a regulatory role for Lp[a] plasma levels in humans with normal renal function, we conclude from our data that substantial amounts of this atherogenic lipoprotein are taken up by the kidney. The underlying mechanisms are unknown at the moment. This study therefore demonstrates for the first time that the human kidney plays an active role in the catabolism of Lp[a]. This may explain the elevated Lp[a] concentrations found in patients with chronic renal insufficiency.

Cerebrospinal fluid (CSF) pharmacokinetics of intraventricular vancomycin in patients with staphylococcal ventriculitis associated with external CSF drainage.

We studied the efficacy and pharmacokinetics of intraventricularly administered vancomycin in three patients with shunt-associated staphylococcal ventriculitis. We instilled 10 mg of the drug intraventricularly every 24 hours. Cerebrospinal fluid (CSF) levels were measured 1 hour after instillation and then every 2 hours. Peak vancomycin levels reached a mean of 292.9 microg/mL. The mean trough levels, measured immediately before readministration of vancomycin, were 7.6 microg/mL; this level has proved to be sufficient for maintaining the necessary steady-state serum concentration of vancomycin. All three patients were cured clinically and bacteriologically, and CSF parameters returned to normal within 5-13 days. No side effects were observed. Our results suggest that intraventricularly administered vancomycin is a valuable therapeutic strategy for treating shunt-associated staphylococcal ventriculitis. In addition, we provide evidence that 10 mg of vancomycin, administered intraventricularly every 24 hours, allows maintenance of therapeutic drug levels in the CSF for at least 24 hours.

New NO-donors with antithrombotic and vasodilating activities, Part 14. 1,3,4-Triazol-1-oles.

Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl substituents in 2,5-position were synthesized and tested for their antithrombotic properties. The 2,5-dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a-inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 mumol/L.

Clinical value of fructose 1,6 bisphosphatase in monitoring renal proximal tubular injury.

The usefulness of the gluconeogenic key enzyme fructose 1,6 bisphosphatase (FBPase), which is localized exclusively in the proximal nephron segment, as a marker compound to monitor injury of the proximal nephron segment during nephrotoxic therapy, was tested in a collective model of male patients treated for testicular cancer. These patients with normal kidney function were submitted to therapy with the nephrotoxic chemotherapeutics carboplatinum and a combination of cisplatinum, etoposide, bleomycin and ifosfamide. The release of FBPase activities into the urine was monitored during the initial two treatments over a period of eight days. The urinary enzyme activities measured were compared to the excretion of the "proximal tubular injury markers" N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin (alpha 1m). The presence of glomerular damage was determined by measurement of urinary excretion rates of albumin (ALB) and IgG. In addition, protein excretion patterns following chemotherapy were monitored. The combined administration of cisplatin, etoposide and ifosfamide resulted in a pronounced proximal tubular injury as shown by the release of FBPase into the urine. This is substantiated by simultaneously increased excretion rates for NAG and alpha 1m. Proximal tubular toxicity was found to be less severe when cisplatin was combined with etoposide and bleomycin and was nearly absent following carboplatinum monotherapy. Carboplatinum only affected glomerular function and resulted in an elevated ALB and IgG excretion. From this model investigation it can be delineated that determination of urinary FBPase activities ensures a sensitive and reliable identification of proximal nephron damage.

Estimation of reference intervals from a SENIEUR protocol compatible aged population for immunogerontological studies.

Because many laboratory values change with age, the study of healthy aging as well as diagnosis of disease in geriatric patients requires specific age-corrected reference intervals. We have established such reference intervals for a healthy population aged 65-74 years by selection of a sample group applying the clinical criteria of the SENIEUR protocol and we have compared them with those of a young control group (20-33 years) fulfilling the same criteria. Significant or minor elevations were seen, e.g. for plasma concentrations of fasting glucose, urea, total and LDL-cholesterol, triglycerides, gamma-glutamyl-transferase, alkaline phosphatase, erythrocyte sedimentation rate and serum neopterin levels. These reference intervals can be used for selecting a SENIEUR compatible population aged between 65 and 74 years. Additionally, plasma lipid parameters (cholesterol, triglycerides) are proposed to be included in the SENIEUR protocol.