5alpha-reductase 2 polymorphisms as risk factors in prostate cancer

Prostate cancer is a significant cause of death in Western countries and is under the strong influence of androgens. The steroid 5alpha-reductase 2 catalyzes the metabolism of testosterone into the more potent androgen dihydrotestosterone in the prostate gland. The enzyme is a target in pharmacological treatment of benign prostatic hyperplasia using specific inhibitors such as finasteride. Makridakis et al. have characterized the V89L and A49T polymorphisms in recombinant expression systems. The L allelic variant has a lower Vmax/Km ratio than the V variant. In the A49T polymorphism, the T variant has an increased Vmax/Km ratio. We performed a population-based case-control study of the impact of the SRD5A2 V89L and A49T polymorphisms on the risk of prostate cancer. We also studied the relation between the genotypes and age at diagnosis, tumor, node, metastasis stage, differentiation grade, prostate specific antigen and heredity. The study included 175 prostate cancer patients and 159 healthy controls that were matched for age. There was an association with SRD5A2 V89L LL genotype and metastases at the time of diagnosis, OR 5.67 (95% CI 1.44-22.30) when adjusted for age, differentiation grade, T-stage and prostate specific antigen. Heterozygous prostate cancer cases that carried the SRD5A2 A49T AT genotype were significantly younger than cases that carried the AA genotype, (mean age 66 years vs 71, P = 0.038). The SRD5A2 V89L and A49T polymorphisms were, however, not associated with altered prostate cancer risk. Further studies of the V89L polymorphism may lead to better understanding of the etiology of prostate cancer metastases.     

The epidemiology of gastric cancer

The epidemiology of gastric cancer is remarkable for both its dramatic decline in incidence over the past century and its continuing presence as the second leading cause of cancer deaths worldwide despite this decline. Factors including increased consumption of fruits and vegetables, and decreased intake of salty foods have largely been credited for the decline. Epidemiologic studies continue to provide data on other gastric cancer risk factors, including associations with Helicobacter pylori infection, as well as dietary factors, tobacco, and alcohol intake. In response to the opposing trends of decreasing distal gastric cancer and increasing gastric cardia adenocarcinoma, studies are beginning to identify gastric cancer risk factors separately by tumor subsite. Future epidemiologic studies that include information on site of origin as well as molecular markers promise to yield more homogeneous classification of case groups, which will enhance identification of underlying disease processes.     

Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma

Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P 相似文献   

Percutaneous endoscopic gastrostomy complications in a tertiary-care center

Since its introduction in 1980 the percutaneous endoscopic gastrostomy (PEG) has become the procedure of choice for establishing enteral access. However, there is still a relatively high complication rate associated with PEG placement. We reviewed the complications associated with PEG placement at our tertiary-care referral center. A retrospective chart review was conducted on patients over 17 years of age undergoing PEG placement between January 1, 1994 and March 1, 1996. Indications for surgery, antibiotic use, and postoperative complications were determined. There were 166 PEGs placed during this time and 27 (16.3%) complications. There was one death (0.6%) directly related to PEG placement. Thirteen patients (7.8%) died within 30 days of PEG placement and an additional 12 patients (7.2%) died before leaving the hospital. Wound infections occurred in nine (5.4%) patients including one case of necrotizing fasciitis. Only four of 153 (2.6%) patients who received preoperative antibiotics developed wound infections, whereas five of 13 (38.5%) patients without antibiotic prophylaxis developed infections. We conclude that percutaneous endoscopic gastrostomy is a safe and effective way of establishing enteral access in most patients. A relatively high mortality rate can be expected as a result of underlying medical problems. Antibiotics should be given to help prevent local wound infections.     

Education,pay, and job status: a national survey of transplant coordinators

To identify education, pay, and job responsibilities, an informal 19-item survey was sent to 1661 transplant coordinators; 424 (26%) were returned. Respondents worked in all phases of transplantation. Education levels varied widely; most respondents had some formal nursing education. Full-time salaries were from $25,000 to $110,000 per year; 67% worked 40 to 50 hours and 19% worked more than 50 hours per week. Of 402 clinical coordinators, 280 (70%) took call, and 122 (30%) did not. Call frequency varied with rotations every second, third, and fourth week; 44% of those taking call did not receive additional on-call pay. Nurse-managed clinics (with physician availability) were the predominant workplace for clinical coordinators. Autonomy and contact with patients were the most liked aspects of the job, and the least-liked aspects were on-call status and paper-work. Increased salary and added support staff ranked top among desired changes in the job. Transplant coordinators appear to be committed professionals who are critical to all endeavors in organ transplantation.     

The Need for Treatment and Satisfaction with Dental Appearance among Young Finnish Adults with and without a History of Orthodontic Treatment

The aim of this investigation was to evaluate orthodontic treatment need and patient satisfaction among young adults living in a city where free-of-charge orthodontic treatment was provided. A total of 281 18- to 19-year-old subjects randomly selected from the population register of the city of Vantaa took part in the study. The drop-out rate was 30%. Treatment need was clinically assessed according to the Index of Orthodontic Treatment Need (IOTN), consisting of a Dental Health Component (DHC) and an Aesthetic Component (AC). Information on previous orthodontic treatment was based on the patient records. Satisfaction of the subjects with their dental appearance and with the orthodontic treatment received was obtained using a questionnaire. The rate of orthodontic treatment among the subjects was 46% (54% for the females and 37% for the males, p < 0.05). 4% had discontinued treatment. A definite need for treatment (DHC 4 to 5/AC 8 to 10) was assessed in 15% of the subjects, and borderline/moderate need (DHC 3/AC 5 to 7) in 36%. No difference in IOTN scores between the treated and untreated subjects was found. Females had significantly more often no treatment need (DHC 1 to 2/AC 1 to 4) compared with males (p < 0.05). The majority of subjects (89%) reported that they were very or quite satisfied with their dental appearance. The odds of being satisfied were significantly higher for the treated subjects (OR = 2.71, p < 0.05) and lower for those at the non-attractive end of the AC scale (OR = 0.14, p < 0.01). Neither gender nor DHC grade significantly affected the odds of being satisfied among the subjects. The results indicate that the majority of young adults in this study were satisfied with their dental appearance regardless of objective treatment need of various degrees. The high treatment rate in relation to unnoticed treatment need calls for reevaluation of priorities in patient selection. Zusammenfassung: Ziel dieser Untersuchung war es, den kieferorthopädischen Behandlungsbedarf und die Zufriedenheit junger Erwachsener zu bewerten, die in einer Stadt leben, in der eine kostenlose kieferorthopädische Behandlung angeboten wurde. Insgesamt nahmen an dieser Studie 281 18- bis 19-jährige Personen teil, die nach dem Zufallsprinzip aus dem Bevölkerungsverzeichnis der Stadt Vantaa ausgewählt wurden. Die Ausfallsrate betrug 30%. Der Behandlungsbedarf wurde gemäß dem "Index of Orthodontic Treatment Need" (IOTN) bewertet, der sich aus dem "Dental Health Component" (DHC) und einem "Aesthetic Component" (AC) zusammensetzt. Anamnestische Daten der Patienten gaben Aufschluss über eine vorangegangene kieferorthopädische Behandlung. Die Zufriedenheit der Personen mit dem ästhetischen Erscheinungsbild ihrer Zähne und mit der kieferorthopädischen Behandlung wurde mittels eines Fragebogens festgestellt. Der Anteil der Personen mit kieferorthopädischer Behandlung betrug 46% (54% Frauen und 37% Männer, p < 0,05). 4% hatten die Behandlung abgebrochen. Ein eindeutiger Behandlungsbedarf (DHC 4 bis 5/AC 8 bis 10) wurde bei 15% der Untersuchten festgestellt, ein grenzwertiger/mäßiger Behandlungsbedarf (DHC 3/AC 5 bis 7) bestand bei 36%. Bei den behandelten und unbehandelten Personen stellte man keinen Unterschied bei den IOTN-Kriterien fest. Bei Frauen bestand wesentlich seltener Behandlungsbedarf (DHC 1 bis 2/AC 1 bis 4) als bei Männern (p < 0,05). Die Mehrheit der Untersuchten (89%) sagte aus, dass sie mit dem ästhetischen Erscheinungsbild ihrer Zähne sehr oder ziemlich zufrieden wären. Die Zufriedenheitsrate war bei den behandelten Personen deutlich höher (OR = 2,71, p < 0,05) und niedriger bei denen, die am unattraktiven Ende der AC-Skala standen (OR = 0,14, p < 0,01). Weder das Geschlecht noch der DHC-Grad beeinflusste signifikant die Zufriedenheitsrate der Untersuchten. Das Ergebnis deutet darauf hin, dass die Mehrheit der jungen Erwachsenen dieser Studie, unabhängig von einem objektiven Behandlungsbedarf verschiedenen Ausmaßes, mit ihrer dentalen Ästhetik zufrieden war. Die hohe Behandlungsquote in Beziehung zu einem nicht begründeten Behandlungsbedarf erfordert eine Neueinschätzung der Prioritäten bei der Auswahl der Patienten.     

Regulation of cyclin expression and cell cycle progression in breast epithelial cells by the helix-loop-helix protein Id1

The helix-loop-helix protein Id1 has been implicated in regulating mammary epithelial cell proliferation and differentiation but the underlying molecular mechanisms are not well characterized. Under low serum conditions, ectopic expression of Id1, but not Id2, allowed continued proliferation of immortalized mammary epithelial cells and breast cancer cells. Conversely, downregulation of Id1 impaired proliferation. The effects of short interfering RNA (siRNA)-mediated downregulation of Id1 were the same as those following downregulation of c-Myc: decreased expression of cyclins D1 and E, reduced phosphorylation of pRb at Ser780 (a site targeted by cyclin D1-Cdk4) and reduced cyclin E-Cdk2 activity. Decreased cyclin D1 expression was an early response to Id1 antisense oligonucleotide treatment. Inhibition of c-Myc function by siRNA, antisense oligonucleotides or a dominant repressor resulted in downregulation of Id1, while ectopic expression of c-Myc resulted in rapid induction of Id1, suggesting that Id1 may be downstream of c-Myc. These data indicate that in mammary epithelial cells, Id1 has cell cycle regulatory functions that are similar to those of c-Myc, and suggest that cyclin D1 may be involved in Id1 regulation of cell cycle progression.     

Pain And Discomfort Associated With Mammography Among Urban Low-Income African–American Women

African–American women have lower rates of breast cancer screening than Caucasian women. Discomfort during mammography may deter women from rescreening. Research to date has focused primarily on Caucasian women. This study examined mammography-associated discomfort among urban, low-income African–American women, and how discomfort influenced rescreening intentions. Using survey data from 530 urban African–American women aged 45 years and older, we assessed sociodemographic, psychological, and health-related predictors of pain or discomfort, and associations between pain or discomfort and intention for rescreening. Seventy-six percent of women reported discomfort; reasons included machine compression (96%), breast size (36%), stature (30%), and roughness by technicians (18%). Intention to rescreen within 2 years was significantly reduced with reporting any discomfort (OR 0.61; 95% CI: 0.38, 0.98), reporting two specific reasons—stature (OR 0.47; 95% CI: 0.31, 0.72) and technician roughness (OR 0.43; 95% CI: 0.26, 0.72), and attributing more sources for pain or discomfort (p for trend = 0.02). Most women reported discomfort; for some, this influenced intended adherence. Offering women the opportunity to control the amount of compression may reduce the pain associated with mammography and subsequently increase compliance.Support for this research was provided by investigator-initiated grant R01 CA066065 to Dr. Klassen from the National Cancer Institute of the National Institutes of Health, and by funding to the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center from the Avon Products Foundation.     

Artefacts in continuous ECG recordings--provoking and preventing manoeuvres

OBJECTIVES: A systematic estimation of the effects of some clinically important artefact provoking and artefact-preventing manoeuvres. DESIGN: A test protocol for the evaluation of technical modifications of continuous ECG recordings was tested in 17 patients. The programme comprised ECG recordings during five artefact-provoking manoeuvres (slight shaking of the ECG cables, rotating shoulders, slight electrode touching, washing, teeth-brushing) and two simple artefact-preventing manoeuvres (taping ECG cables and covering electrodes with paper cups). RESULTS: The artefact-provoking manoeuvres induced a substantial increase in artefactual ECG. The artefact-preventing manoeuvres only incompletely prevented this increase. CONCLUSION: There is a great need of technical improvements to reduce the distortion of ECG by artefacts. The test protocol developed by us exposes a broad spectrum of different categories of ECG qualities and is therefore suitable for evaluating technical improvements concerning artefactual ECG.