The modified Glasgow prognostic score in prostate cancer: results from a retrospective clinical series of 744 patients

<p>Background: As the incidence of prostate cancer continues to rise steeply, there is an increasing need to identify more accurate prognostic markers for the disease. There is some evidence that a higher modified Glasgow Prognostic Score (mGPS) may be associated with poorer survival in patients with prostate cancer but it is not known whether this is independent of other established prognostic factors. Therefore the aim of this study was to describe the relationship between mGPS and survival in patients with prostate cancer after adjustment for other prognostic factors.</p> <p>Methods: Retrospective clinical series on patients in Glasgow, Scotland, for whom data from the Scottish Cancer Registry, including Gleason score, Prostate Specific Antigen (PSA), C-reactive protein (CRP) and albumin, six months prior to or following the diagnosis, were included in this study.</p> <p>The mGPS was constructed by combining CRP and albumin. Five-year and ten-year relative survival and relative excess risk of death were estimated by mGPS categories after adjusting for age, socioeconomic circumstances, Gleason score, PSA and previous in-patient bed days.</p> <p>Results: Seven hundred and forty four prostate cancer patients were identified; of these, 497 (66.8%) died during a maximum follow up of 11.9 years. Patients with mGPS of 2 had poorest 5-year and 10-year relative survival, of 32.6% and 18.8%, respectively. Raised mGPS also had a significant association with excess risk of death at five years (mGPS 2: Relative Excess Risk = 3.57, 95% CI 2.31-5.52) and ten years (mGPS 2: Relative Excess Risk = 3.42, 95% CI 2.25-5.21) after adjusting for age, socioeconomic circumstances, Gleason score, PSA and previous in-patient bed days.</p> <p>Conclusions: The mGPS is an independent and objective prognostic indicator for survival of patients with prostate cancer. It may be useful in determining the clinical management of patients with prostate cancer in addition to established prognostic markers.</p&gt

Impact of hiatal hernia on histological pattern of non-erosive reflux disease

BACKGROUND: Hiatus hernia (HH) has major pathophysiological effects favoring gastroesophageal reflux and hence contributing to esophageal mucosa injury, especially in patients with severe gastroesophageal disease. However, prospective studies investigating the impact of HH on the esophageal mucosa in non-erosive reflux disease (NERD) are lacking. This study evaluated the association between the presence of (HH) and the histological findings in symptomatic patients with NERD. METHODS: Fifty consecutive patients with gastroesophageal reflux disease (GERD) were enrolled. After conventional endoscopy, Lugol solution was applied and biopsy specimens were obtained. Histological parameters including basal zone hyperplasia, papillary length and cellular infiltration were evaluated. The chi-square test with Yates' correlation was used for comparing discrete parameters between groups. However, Fisher's exact probability test was used where the expected frequencies were lower than 5. Wilcoxon's test for unpaired samples was preferred in cases of semi-quantitative parameters. RESULTS: The presence of HH along with more severe findings (0.01 <P < 0.05) was confirmed in 18 patients. NERD was observed in 29 (58%) patients. Basal zone hyperplasia and loss of glycogen accompanied HH in all cases, and the correlation was significant in NERD (P < 0.001). The remaining histological patterns were similar between erosive reflux disease and NERD in the presence of HH. CONCLUSION: The presence of HH is correlated with more severe endoscopy findings, and predisposes for severe histological abnormality in cases of NERD

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

The Islamic Law in the Historical Study

Dalam kajian tentang sejarah awal Islam dan agama di dunia Barat, Islam dipandang sebagai agama \u27\u27dalam sejarab". Melaiui pandangan ini, para sarjana mempelajari sejarah awal Islam, di antaranya, dengan menggunakan meiode analisa kritik terbadap sumber-sumber sejarah termasuk kepusiakaan selain Islam dijadikan sebagai sumber dan bukti sejarah. Sejak itu pula hukum Islam dikaji melaiui pendekatan yang sama. Melaiui pendekatan ini diyakini bahwa hukum Islam mengandung tradisi-tradisi keagamaan khususnya di wilayab limur dekat yang ada sebeium Islam, dan dipandang sebagai suatu perkembangan yang berkelanjutan. Sebagaimana hasii kajian daripada Patricia Crone dan Gordon D. Newby menunjukkan bahwa di antara tradisi-tradisi keagamaan dimaksud, saiah satunya, adalab hukum Yahudi. Crone memberikan contoh qasama khususnya yang ada pada mazhab Maiiki dan mengktaim bahwa qasama dimaksud merupakan salah satu tradisi hukum yang ada pada orang-orang Yahudi. Sedangkan Newby memberikan contoh tentang penentuan orang band sebagai laki-iaki atau sebagai perempuan dalam hubungannya dengan pembagian kewarisan yang ada pada catatan \u27Amirb. Zarib di daiam sirah Ibnu Ishaq, dan mengktaim juga bahwa catatan tersebut berasai dari hukum Yahudi. Sebaliknya, pendekatan ini merupakan salah satu pendekatan yang ada dalam kajian hukum Islam dan sangat baik dipakai untuk mencari keseimhangan dan menunjukkan bahwa walaupun terdapat kesamaan antara hukum Islam dengan hukum-hukum yang lain, proses sejarab perkembangan hukum Islam itu sendiri sangat berbeda dan mempunyai karakteryang khusu

Extending basic principles of measurement models to the design and validation of Patient Reported Outcomes

A recently published article by the Scientific Advisory Committee of the Medical Outcomes Trust presents guidelines for selecting and evaluating health status and health-related quality of life measures used in health outcomes research. In their article, they propose a number of validation and performance criteria with which to evaluate such self-report measures. We provide an alternate, yet complementary, perspective by extending the types of measurement models which are available to the instrument designer. During psychometric development or selection of a Patient Reported Outcome measure it is necessary to determine which, of the five types of measurement models, the measure is based on; 1) a Multiple Effect Indicator model, 2) a Multiple Cause Indicator model, 3) a Single Item Effect Indicator model, 4) a Single Item Cause Indicator model, or 5) a Mixed Multiple Indicator model. Specification of the measurement model has a major influence on decisions about item and scale design, the appropriate application of statistical validation methods, and the suitability of the resulting measure for a particular use in clinical and population-based outcomes research activities

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

The treatment and outcomes of early-stage epithelial ovarian cancer: have we made any progress?

The objective of this study is to determine the progress and trends in the treatment and survival of women with early-stage (I–II) epithelial ovarian cancer. Data were obtained from the SEER database between 1988 and 2001. Kaplan–Meier and Cox regressions methods were employed for statistical analyses. Of the 8372 patients, the median age was 57 years (range: 12–99 years). A total of 6152 patients (73.4%) presented with stage I and 2220 (26.5%) with stage II disease. Over the periods 1988–1992, 1993–1997, and 1998–2001, 3-year disease-specific survivals increased from 86.1 to 87.2 to 88.8% (P=0.076). The number of patients that underwent lymphadenectomy has increased significantly from 26.2 to 38.7 to 54.2% over the study period (P<0.001). Of those patients who underwent staging procedures with lymphadenectomy, there was no improvement in survival over the three study periods (from 93.2 to 93.5 to 93.1%; P=0.978). On multivariate analysis, younger age, nonclear cell histology, earlier stage, lower grade, surgery, and lymphadenectomy were significant independent prognostic factors for improved survival. After adjusting for surgical staging with lymphadenectomy, the year of diagnosis was no longer an important prognostic factor. In conclusion, the use of lymphadenectomy during surgery for early-stage ovarian cancer has doubled over the last 14 years. The marginal improvement in survival demonstrated over time is potentially attributed to the increased use of staging procedures with lymphadenectomy

Safety of liver resection and effect on quality of life in patients with benign hepatic disease: Single center experience

<p>Abstract</p> <p>Background</p> <p>Although liver resection has long been established for selected patients with benign hepatic disease, the success of surgical treatment of these patients cannot be evaluated exclusively through postoperative morbidity and mortality. Therefore, the aim of the study was to prove the safety of liver resection in the treatment of benign liver tumors and to evaluate the effect of surgical treatment on the patients' qauality of life.</p> <p>Methods</p> <p>A total of 146 patients who underwent liver resection because of benign liver tumors were included in this study. Postoperative outcome was assessed and patients evaluated their quality of life before surgery and at the present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30).</p> <p>Results</p> <p>The rate of serious (> grade 2) complications was 4.1% with no postoperative death. The quality of life assessment revealed an overall improvement of general health status after resection (0.7 vs. 0.56, p < 0.001) and additionally a significant reduction of 6 out of 9 symptoms. Furthermore, compelling benefits in the patients' social and emotional coping could be detected after surgery.</p> <p>Conclusions</p> <p>Liver resection for benign liver disease is a safe procedure and leads to a significant improvement of quality of life in selected patients.</p

Morbidity, life style and psychosocial situation in cancer survivors aged 60-69 years: results from The Nord-Trøndelag Health Study (The HUNT-II Study)

<p>Abstract</p> <p>Background</p> <p>Due to considerable health status differences in the elderly population, research limited to narrow age-spans might be an advantage. In this population-based controlled study we compare short-term (<5 years) (STS) and long-term (≥5 years) (LTS) cancer survivors and cancer-free controls aged 60-69 years from two Norwegian health registers; the Health Survey of North-Trøndelag County (HUNT-2 study) and the Cancer Registry of Norway (CRN). We examined possible factors associated with being cancer survivor.</p> <p>Methods</p> <p>Among 9,089 individuals aged 60-69 who participated in HUNT-2, 334 had been diagnosed with invasive primary cancer from 1 month to 42 years before HUNT-2 according to CRN and self-report. An overall random sample of controls without cancer five times larger than the sample of cases (N = 1,670) were drawn from the parent cohort.</p> <p>Results</p> <p>The cancer sample comprised 128 STS and 206 LTS. For most variables no significant differences were observed between LTS and STS. LTS were significantly more women, and cases with gynaecological cancer, with physical impairment and more thyroid diseases compared to STS. When comparing all the survivors with controls, the survivors showed significantly higher rate of pensioning, decreased self-rated health, more physical impairment and thyroid diseases, daily use of medication and psychotropics and higher level of anxiety and Framingham Risk score. Multivariate logistic regression analysis showed that increasing age, being female, physical impairment and thyroid diseases all were significantly associated with being survivor versus controls.</p> <p>Conclusion</p> <p>STS and LTS showed mostly similar situation. Compared to controls, the survivors reported somewhat poorer physical and mental health, but these differences were of doubtful clinical significance.</p