ObjectiveTo validate the authors' initial hypothesis-generating observation that eukaryotic initiation factor 4E (eIF4E) protein elevation predicts a higher cancer recurrence rate in patients with stage 1 to 3 breast cancer. Summary Background DataTumor size and nodal status continue to be the two most important independent prognostic markers in breast cancer, despite well-documented limitations. In a previous smaller retrospective study, eIF4E, important in the regulation of protein synthesis of mRNAs with long or complex 5' untranslated regions, appeared promising as an independent predictor of breast cancer recurrence. MethodsSpecimens and clinical data from 191 patients with stage 1 to 3 breast cancer were accrued prospectively. Data collected include stage of disease, tumor grade, age at diagnosis, and menopausal status. Endpoints measured were disease recurrence and cancer-related death. eIF4E protein level was quantified using Western blot analysis. Immunohistochemical staining was used to determine estrogen receptor, progesterone receptor, and HER-2/neu receptor status. Statistical analysis include Cox proportional hazards model, log-rank test, Kaplan-Meier survival curve, Fisher exact test, and t test. ResultsPatients were divided into three groups based on tertile distribution of eIF4E: low, defined as less than 7.5-fold elevation (n ϭ 64); intermediate, defined as 7.5-to 14-fold elevation (n ϭ 61); and high, defined as more than 14-fold elevation (n ϭ 66). The relative risk for cancer recurrence with intermediate elevation was 4.1 times that of patients with low elevation. For patients with high elevation, the relative risk for recurrence was higher, at 7.2 times that of the low group. The relative risk for cancer-related death for high elevation was 7.3 times that of patients with low eIF4E. Using multivariate analysis, high eIF4E remained an independent predictor of cancer recurrence after adjusting for tumor size, tumor grade, nodal disease, estrogen receptor status, progesterone receptor status, and menopausal status. ConclusionsHigh eIF4E is an independent predictor of cancer recurrence in patients with stage 1 to 3 breast cancer. The relative risk for cancer recurrence increases with eIF4E protein elevation. High eIF4E elevation is also associated with an increased relative risk for cancer-related death.To date, the two most important independent prognostic markers in breast cancer continue to be tumor size and nodal status.1,2 However, systemic failure can and does occur in patients with small, node-negative tumors.3 Approximately two thirds of invasive breast carcinomas present without evidence of axillary lymph node involvement, but at least 25% of these carcinomas eventually recur.1,3 Conversely, more than 30% of node-positive breast carcinomas do not develop recurrent disease.1 These inherent deficiencies in the TNM staging system have necessitated the search for a prognostic marker in breast carcinoma, independent of tumor size and nodal status.Malignant transformation is a multistep proce...
The objective of this study was to investigate the clinical manifestations and diagnostic studies used to evaluate Crohn's patients with enterovesical fistulas (EVFs) and to assess outcome after surgical intervention. This is a ten year multi-institutional retrospective chart review of patients with Crohn's disease. Of 400 patients identified with Crohn's disease eight (2%) were diagnosed with EVF. The mean age at diagnosis was 27 years. No patients had prior surgeries for Crohn's. Duration of symptoms ranged from 6 months to 15 years. There were seven ileovesical and one colovesical fistula identified. One patient had associated perianal disease. Three had concomitant enteroenteral fistulae. Clinical features included pneumaturia in seven patients (88%), fecaluria in three (38%), hematuria in five (63%), and urinary tract infection symptoms in seven (88%). Diagnostic studies included CT scan in six, barium or gastrografin enema in four, and cystoscopy in four. Surgical therapy involved resection of the affected bowel. The bladder defect was closed primarily in two layers in all patients using absorbable suture, with omental patch in four. Two patients underwent ileostomy and one underwent colostomy, all taken down within 6 months. There were no bladder leaks and no anastamotic leaks. There were no perioperative deaths. The mean postoperative stay was nine days. The mean follow-up was 39 months. We conclude that pneumaturia is a strong clinical indicator of EVF. CT has been valuable in identifying gas within the bladder in these patients. Cystoscopy has proven useful in identifying the fistulous tract and in evaluation of the ureters. The presence of an EVF should heighten suspicion as to the presence of concomitant enteroenteral fistulae. Barium or gastrografin studies are useful in this capacity. Surgical treatment of EVFs should include resection of affected bowel. The bladder defect can safely be closed using absorbable suture.
62 tissue specimens with the only diagnosis benign nephrosclerosis (or benign nephrosclerosis with transition to secondary malignant nephrosclerosis) were investigated attempting to correlate morphological findings (relative interstitial volume of the renal cortex, types of hyalinisation and kinds of periglomerular changes, vessel index) with each other and with the serum creatinine concentration as a parameter of renal function. There are significant correlations in form of exponential and parabolic functions between relative interstitial volume of the renal cortex and the serum creatinine concentration at the time of biopsy. Furthermore 5 types of glomerular and periglomerular changes, which could be discriminated, seem to influence renal function in a different way and at different stages of the disease. An additional factor are the arteriolar changes. There are positive rank correlations between vessel index and serum creatinine concentration as well as between vessel index and relative interstitial volume. In cases with a higher percentage of hyalinized glomeruli more pronounced arteriolar lesions (partly alterations which can be found in secondary malignant nephrosclerosis) were observed. No connections seem to exist between mean blood pressure and the mentioned morphological and functional parameters. The reduction of renal function seems to be caused by tubular and interstitial factors: the often observed atrophy of tubules in fibrotic areas possibly impairs resorptional capacity. The mechanisms of the glomerular-tubular-balance may lead to a diminished glomerular filtration. On the other hand alterations of the capillaries may induce perivascular edema, which, if not reabsorbed, leads to interstitial fibrosis. The produced collagen fibres may reduce the cross sectional area of the postglomerular vessel network. This may lead to a slowing of the renal cortical and glomerular blood flow, thus inducing an increase of the serum creatinine concentration. Weighing all factors, the interstitial fibrosis seems to be the most important.
Efll mflll ¶gQ j Form Approved REPORT DOCUMENTATION PAGE OMB No. 0704-0188Public re ... rt d ourden tor thtt Kollectiln of information ,s estimate• to iveraqe i hu r per •e:orse tncrludi nr the time for reviewing instructions. searrnltg ex $sting data sources, gathering and -m a ntrnq the data needed., and .Omnletittq and te-P•i.nq t" ýl l.eclwon of intormation Send comments regarding this burdent estmate or ýtnt Othpr The authors, a group of 18 veteran space operations officers, explored the concept of placing a permanentl3rt manned station on Mars -Project Ares. Using a five phase plan involving an early moon base and thred scientific missions to Mars followed by cargo missions and eventually manned trips to the planet, the authors analyzed, designed, and documented their approach. The report focuses on the second phase of the project --scientific expansion of our knowledge of Mars and proof of a reliable transportation system. Among the subjectsi discussed in the report are management, mission profile and environment, and mission systems. The latteri subject contains a variety of systems proposed by various authorities in the space industry and selected to fulfill the unique requirements of the project. Because this phase is an integral part of the project, emphasis was on2 reusability and versatility.14. ... Our goal is to build on America's pioneer spirit and develop our next frontier.. .space. Nowhere do we so effectively demonstrate our technological leadership and ability to make life better on Earth.. .Our progress in space-taking giant steps for all mankind-is a tribute to American teamwork and excellence.. .We can follow our dreams to distant stars, living and working in space for peaceful, economic, and scientific gain. List of Tables President Ronald Reagan State of the Union Address 25 January 1984The first generation of space-probes has revealed so much strangeness and grandeur on our neighboring worlds that, as soon as the technical means are available, men will certainly visit them. And having done this, they will find reasons for living there-as on this earth they have established themselves in such improbable spots as the South Pole and the bottom of the ocean. Space itself, to the considerable surprise of most people, has turned out to be a benign environment; it is only the planets that are hostile. Even this was anticipated almost a century ago by Tsiolkovsky; he regarded the weightless realm of space as man's ultimate home.. .The escape from gravity which we have all known in our dreams may remind us of life's origins in the ocean; but it may also anticipate a far longer future in space. Cosmonaut-artist Alexei Leonov, the first man to step out of a space capsule and to float in the void, entitled his book of paintings: The Stars are Waiting.Arthur C. Clarke Sri Lanka 1980 viii / L Executive Summary Project ObjectivesThe objectives for the GSO-92D design team are to:1. Conduct preliminary research into a space-related systems engineering problem utilizing a project management approach.2....
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