Ecotropic viral integration site 1, a novel oncogene in prostate cancer.

Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in men in the western world. Mutations in tumor suppressor genes and in oncogenes are important for PCa progression, whereas the role of stem cell proteins in prostate carcinogenesis is insufficiently examined. This study investigates the role of the transcriptional regulator Ecotropic Viral Integration site 1 (EVI1), known as an essential modulator of hematopoietic and leukemic stem cell biology, in prostate carcinogenesis. We show that in healthy prostatic tissue, EVI1 expression is confined to the prostate stem cell compartment located at the basal layer, as identified by the stem cell marker CD44. Instead, in a PCa progression cohort comprising 219 samples from patients with primary PCa, lymph node and distant metastases, EVI1 protein was heterogeneously distributed within samples and high expression is associated with tumor progression (P<0.001), suggesting EVI1 induction as a driver event. Functionally, short hairpin RNA-mediated knockdown of EVI1 inhibited proliferation, cell cycle progression, migratory capacity and anchorage-independent growth of human PCa cells, while enhancing their apoptosis sensitivity. Interestingly, modulation of EVI1 expression also strongly regulated stem cell properties (including expression of the stem cell marker SOX2) and in vivo tumor initiation capacity. Further emphasizing a functional correlation between EVI1 induction and tumor progression, upregulation of EVI1 expression was noted in experimentally derived docetaxel-resistant PCa cells. Importantly, knockdown of EVI1 in these cells restored sensitivity to docetaxel, in part by downregulating anti-apoptotic BCL2. Together, these data indicate EVI1 as a novel molecular regulator of PCa progression and therapy resistance that may control prostate carcinogenesis at the stem cell level.

Fibrin glue for securing the mesh in laparoscopic totally extraperitoneal inguinal hernia repair: a study with a 40-month prospective follow-up period.

BACKGROUND: Anchoring the mesh in laparoscopic totally extraperitoneal groin hernia repair (TEP) with human fibrin glue has theoretical advantages. However, these have been supported and reported previously only in animal studies. Before the initiation of large patient trials, the authors wanted to confirm the feasibility, assess the costs, and rule out any flagrant short- and long-term adverse effects of fibrin glue usage in a small series of patients. METHODS: Nine consecutive TEP repairs with fibrin glue mesh fixation were performed. The perioperative and postoperative outcomes at 1, 16, and 40 months were compared with those for a control group of 96 stapled repairs. RESULTS: Gluing was easy and is less expensive than stapling. No fibrin glue-related adverse effects were found. The overall outcome was similar to that for stapled repairs, with no indication that the glued repairs were inferior. CONCLUSIONS: Fibrin glue seems to be a reasonable, feasible, and maybe even competitive alternative to the standard tissue-penetrating mesh fixation. The results of this study justify launching larger trials.

Chromatographic, capillary electrophoretic and matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of urinary modified nucleosides as tumor markers.

Modified nucleosides are formed posttranscriptionally in RNA. During RNA turnover free modified nucleosides are formed which circulate in the blood stream and are excreted in the urine. Their levels are increased in a number of malignant diseases, and they can be used in clinical chemistry as tumor markers. The analysis includes the isolation of the nucleosides from urine with phenylboronate gel and their separation and quantitation by HPLC on C18 columns or by capillary electrophoresis on uncoated columns applying a sodium dodecyl sulfate-borate-phosphate buffer. Identification of the nucleosides is performed with matrix-assisted laser desorption ionization time-of-flight mass spectrometry including post source decay spectra. In two clinical studies the diagnostic value of urinary modified nucleosides is investigated, in a study on children with leukemia and other malignant diseases and a study on women with breast cancer. Candidate markers are pseudouridine, 1-methylguanosine, N2-methylguanosine, 3-methyluridine and 1-methyl-inosine.

Age-dependence of urinary normal and modified nucleosides in childhood as determined by reversed-phase high-performance liquid chromatography.

Modified nucleosides have been characterized as tumor markers for a number of malignant diseases. In order to use these markers in children, the age-dependence of the nucleoside levels in healthy children has to be established and taken into account in diagnostic decisions. In this study, the levels of 12 normal and modified nucleosides in urine of 166 healthy children and adolescents with an age between 1 day and 19 years are determined by reversed-phase HPLC, and age-dependent reference ranges are defined. The urinary nucleoside concentrations are related to the creatinine concentrations, which allows the use of randomly collected urine samples. All nucleoside levels in urine of children decrease with age, most pronounced during the first 4 years of life, and the age-dependence of the reference values of the individual nucleosides can be approximated by a mathematical function y = b(0) + b(1) (1/x) with the regression coefficients b(0) and b(1,) the nucleoside levels y and the age x between 1 year and 19 years. In the very young children, the shifts in the nucleoside concentrations are more differentiated. Starting with low levels on the first day of life, the concentrations of all studied nucleosides rise up to an age of 1-2 months, when they reach their absolute maximum for all age periods, and then decrease.

Disease management strategies: managing care giving in managed care.

The rapid rate of change in health care delivery systems has challenged and troubled health care providers. Some new health care delivery systems primarily emphasize the economics of medical care and leave providers with a sense that their profession has strayed from its mission. In addition, there is an increasing demand by payers and the public for public accountability for the quality and expense of clinical services. One response to these changes in health care is the use of disease management strategies. There is a growing body of knowledge regarding disease management strategies and practice guidelines in the literature. This article discusses how a provider group can implement improvement in the clinical process successfully by applying techniques of disease management.

[Spread and control of methicillin resistant Staphylococcus aureus in a department of dermatology]. / Spredning og kontrol af methicillinresistente Staphylococcus aureus i en hudafdeling.

Patients with skin diseases caused a spread of methicillin-resistant Staphylococcus aureus (MRSA) to 17 patients in our Department of Dermatology, because of their heavily scaly skin. Patients with severe dermatosis are regularly treated with dicloxacillin. The resistance of bacteria strain concerned suggests a selection because of the use of dicloxacillin in the Department. The strain is sensitive to gentamicin, which differentiates it from strains imported from abroad. Increased hygienic precautions, isolation of infected patients, staff and management efforts and a close contact with the microbiologists prevented MRSA from spreading to other hospital wards.

A case of total peripheral aneosinophilia associated with complete deficiency of myeloperoxidase.

Complete and permanent absence of peripheral eosinophilic granulocytes was observed in a patient also presenting with total myeloperoxidase deficiency. The anomaly was suspected because of complete absence of the eosinophilic cluster in the display of a H*3 Technicon hematological automate and was confirmed by traditional staining of more than 100,000 leukocytes. A severe infectious problem during adolescence could be related to MPO deficiency in this patient. No specific disorder attributable to aneosinophilia was however observed subsequently.

A case of eosinophil peroxidase deficiency.

A case of eosinophil peroxidase deficiency is described after fortuitous detection by the H*3 Technicon hematological analyzer. From the cytochemical aspect total deficiency is admitted. The abnormality is thought to be extremely rare in a well-mixed population as exists in the Grand-Duchy of Luxembourg.

The politics of caring: the role of activism in primary care.

The role of activism in primary care practice, inquiry, and theory development is illustrated through the description of a feminist cooperative inquiry group's deconstruction of menarche education. The development of the emancipatory inquiry method of activist nursing inquiry and its relationship with feminist process is described. The value of feminist process in activist primary care inquiry and practice is examined. A theory of primary caring is inductively gleaned from the research and compared to other caring theories. Connection, commitment, consistency, change, and community are identified as being components of primary caring. A community perspective on primary care is advocated.

Microbial biocatalysis in the generation of flavor and fragrance chemicals.

Microbial biocatalysis is used in the commercial production of many flavor and fragrance chemicals. Bulk flavoring chemicals such as citric acid, high fructose corn syrup, and glutamic acid are produced in millions of pounds annually using microbial processes. In the past few years, biocatalysis has also begun to play an increasingly important role in the production of many flavor and fragrance aroma chemicals. Microbial processes have traditionally played an integral role in the development of complex mixtures of flavor and aroma chemicals since the discovery of beer, wine, cheese, and soy sauce thousands of years ago. Today, contemporary microbiological techniques are being increasingly applied to enhance the efficiency of many microbial biocatalysts for the production of specific flavor and fragrance chemicals. However, to ensure commercial implementation of these new microbial processes, much more needs to be learned about the basic biochemistry and genetics of these novel biocatalysts.

Student views of the school nurse's role in a secondary school condom availability program.

PIP: In Massachusetts, the school committee of a Boston suburb's school board agreed to start a condom availability program at the community's 2 high schools. A nurse researcher conducted 11 focus groups with 112 students to determine students' attitudes and feelings, so they can be incorporated in designing the program. Most students were White, college-bound, and professional-class. The nurse grouped most students by age, gender, and academic tracking into homogeneous groups. A common thread throughout the discussions was a need for respect from adults. Every focus group talked a lot about the risk of humiliation and loss of respect of adults if they took condoms. Students suggested that they would not use the program if it required individual counseling. Overall, the students were concerned about the school nurse's role in safer sex counseling. Sexually active females conveyed a positive relationship with the school nurse, however. The lack of consistent nursing staff contributed to students' doubts about building a relationship with the nurse. Students clearly identified an adult with whom they could feel comfortable talking about sexual matters as someone who would be relaxed, nonjudgmental, knowledgeable, and available for discussion. Based on these findings, the nurse researcher recommended that school nurses have more time to enhance skills in effective and sensitive sexuality counseling and devote more time to counseling and HIV prevention education. She also suggested that schools include more parent and student sexuality education. Developmentally appropriate HIV prevention education should be provided to all students in both junior and senior high schools each year. Final recommendations were intensive inservice education for school nurses, anonymous condom availability, and identification of other school and community personnel to support school nurses.^ieng

Acute exacerbations of COPD. How to evaluate severity and treat the underlying cause.

Acute exacerbations of chronic obstructive pulmonary disease occur often. Severity should be established by signs and symptoms and by reference to baseline pulmonary function test results when necessary. If the exacerbation is mild to moderate, treatment should include antibiotics, theophylline, beta agonists, and mucolytics. Severe exacerbations should be treated with these agents plus supplemental oxygen, intravenous corticosteroids, and, when appropriate, intubation and mechanical ventilation.

Glutathione-independent isomerization of maleylpyruvate by Bacillus megaterium and other gram-positive bacteria.

Maleylpyruvate, the ring fission product of gentisic acid, was found to be isomerized to fumarylpyruvate without a requirement for glutathione by an enzyme activity found in cell extracts of m-hydroxybenzoate-grown Bacillus megaterium 410. The isomerization reaction was detected as a shift in the absorbance maximum from 330 nm, the maximum for maleylpyruvate, to 345 nm, the maximum for fumarylpyruvate, when assayed at pH 8.0. Ammonium sulfate precipitation and dialysis of B. megaterium cell extracts resolved the isomerase activity from low-molecular-weight compounds such as glutathione but did not eliminate the isomerase activity. Iodoacetate and p-chloromercuribenzoate were potent inhibitors of the isomerase from B. megaterium. However, N-ethylmaleimide and iodoacetamide did not significantly inhibit this activity. In addition, fumaric acid was demonstrated as a product of gentisate oxidation by dialyzed cell extracts of B. megaterium. Glutathione-independent maleylpyruvate isomerases with properties similar to the isomerase found in B. megaterium were also found in other genera of gram-positive organisms. Eleven different organisms representing the genera Bacillus, Arthrobacter, Corynebacterium, Nocardia, and Rhodococcus were all found to possess this novel type of glutathione-independent maleylpyruvate isomerase.

Glutathione-independent maleylacetoacetate isomerase in gram-positive bacteria.

Nocardia globerula CL1 produced a glutathione-independent maleylacetoacetate isomerase after growth on L-tyrosine. Partial purification of this isomerase demonstrated its independence of low-molecular-weight cofactors such as glutathione. Similar glutathione-independent maleylacetoacetate isomerases were present in three other gram-positive bacteria grown on tyrosine.