Small molecule inhibitor of TLR4 inhibits ovarian cancer cell proliferation: new insight into the anticancer effect of TAK-242 (Resatorvid)

Cancer Chemotherapy and Pharmacology - Despite all advances in the treatment of ovarian cancer (OC), it remains the most lethal gynecological malignancy worldwide. There are growing amounts of...     

Integrated approach to construction and maintenance of prosthetic arteriovenous access for hemodialysis

Autogenous arteriovenous access is the preferred access for hemodialysis patients with end-stage renal disease but is not feasible in a significant number of patients. The creation of a prosthetic arteriovenous access (PAVA) for hemodialysis using expanded polytetrafluoroethylene is technically simple and the short-term results are usually good, but the PAVA's 1-year patency rate is low (less than 60% in many centers). We have developed an integrated approach for the creation and maintenance of PAVAs, under the direction of a dedicated vascular access surgeon, involving preoperative imaging, anesthetic and surgical techniques, and a postoperative graft surveillance program, to improve patency rates. The design used was a prospective nonrandomized study. Between January 1, 1999 and December 31, 2001, 158 PAVAs were created (37.7% of the 419 fistulae created during this period). High-resolution duplex ultrasonography was added to careful clinical assessment in planning and follow-up of the dialysis access. The preferred method of PAVA creation was the forearm loop using tapered 4 to 7 mm stretch expanded polytetrafluoroethylene. After surgery, patients entered a program of close follow-up and regular graft surveillance and maintenance. Prophylactic surgical revisions and endovascular interventions were performed routinely according to ultrasonography findings to prevent thrombosis. Thrombolysis and thrombectomy were performed without delay when the PAVA thrombosed, minimizing the use of central venous access and salvaging the central veins. No patients were excluded from the study. One-, 2-, and 3-year assisted primary patency rates (including patients without occlusion but who were judged to require prophylactic revision) were 65%, 54.1%, and 48.8%, respectively. With surveillance-directed surgical revisions and endovascular treatment before or after occlusion, the 1-, 2-, and 3-year secondary patency rates (functional patency) were 91.4%, 84.3%, and 78.5%. Of the 158 grafts, 110 never occluded during the study period. There were 155 interventions in 74 PAVAs: 30 surgical revisions, 63 prophylactic endovascular procedures, and 52 instances of thrombolytic therapy combined with percutaneous transluminal angioplasty. The use of prosthetic arteriovenous access for hemodialysis, when autogenous arteriovenous access is not feasible, can still be associated with excellent long-term patency, in spite of previously published poor results, as long as good planning, close follow-up, and aggressive intervention (when indicated) are carried out.     

Pediatric trauma center verification improves quality of care and reduces resource utilization in blunt splenic injury

Purpose

We sought to evaluate value impact of transition from an adult trauma center treating children (ATC) to a verified pediatric trauma center (PTC) in children with blunt splenic injury (BSI).

The nature of the superior sinus venosus defect

The location, and morphology, of the superior sinus venosus interatrial communication remains contentious. As part of a clinical study, we examined anatomic specimens and echocardiograms so as to clarify the arrangement of the normal atrial septal structures, and compared them with the arrangement found in the superior sinus venosus defect. The pathognomonic diagnostic criterion in the abnormal hearts was overriding of the intact muscular rim of the oval fossa by the mouth of the superior caval vein. This muscular rim is, in reality, a tube of myocardium which encloses a core of extracardiac adipose tissue. Understanding of this anatomic conundrum clarifies the understanding of the structures of both the normal atrial septum and sinus venosus defects. Clin. Anat. 11:349–352, 1998. © 1998 Wiley-Liss, Inc.     

Anatomical criteria for the diagnosis of sinus venosus defects.

BACKGROUND: The diagnosis of sinus venosus defects remains a matter of debate. It is crucial to provide solid anatomical criteria, by identifying the very nature of the atrial septum relative to sinus venosus defects, to diagnose and differentiate them from other interatrial communications. OBJECTIVE: This study was designed to reestablish the anatomical criteria for the diagnosis of sinus venosus defects. METHODS: Five specimens with sinus venosus defects from the cardiopathological museum were examined. Study of the abnormal hearts was supplemented by examining the extent and structure of the atrial septum in 10 normal hearts. The echocardiograms and surgical notes were reviewed from 18 patients seen between July 1991 and August 1996 at the Royal Brompton Hospital in London diagnosed preoperatively to have a sinus venosus defect. RESULTS: The nature of the oval fossa and its muscular borders were identified in the normal hearts. In all three autopsied specimens of the superior variety of sinus venosus defect, the mouth of the superior caval vein was overriding the intact muscular anterosuperior border of the oval fossa. Two specimens thought initially to have the inferior variety of sinus venosus defect were re-classified as having defects within the oval fossa as it was the deficient oval fossa itself, rather than its intact muscular border, that was overridden by the mouth of the inferior caval vein. Sixteen patients had been diagnosed echocardiographically as exhibiting the superior variant of the defect. Retrospective review showed overriding of the superior caval vein across the upper rim of the oval fossa in 12 patients. These findings were confirmed by surgery in 11 patients with the 12th awaiting operation. Overriding of the fossa by the caval vein was not found in the other four patients. Surgery in all of these showed the defect to be within the oval fossa. In two patients diagnosed echocardiographically as having inferior defects, the surgical findings confirmed a biatrial connection of the inferior caval vein in one patient, the findings in the second were equivocal. CONCLUSIONS: The key anatomical criterion for the diagnosis of sinus venosus defects is overriding of the mouth of the superior or inferior caval vein across the intact muscular border of the oval fossa. The interatrial communication is then formed within the mouth of the overriding vein, and is outside the confines of the oval fossa.     

Induction of chromosomal aberrations by the rhodium(III) complex cis-[Rh(biq)(2)Cl(2)]Cl in cultured human lymphocytes

The genotoxicity of the rhodium(III) complex cis-[Rh(biq)(2)Cl(2)]Cl (complex R) in cultured human lymphocytes was studied using the chromosome aberrations (CAs) assay. Lymphocyte cultures were initiated from two adult healthy non-smoking male volunteers and were exposed to the complex for a duration of 3 or 20 h prior to cell collection. The reduction in mitotic indices (MI) and the induction of CAs represented the toxic and clastogenic effects of the different treatments, respectively. Complex R proved to be an intermediate toxic clastogen with a MI(50) of 1.0 microg/ml and a minimum positive dose (MPD) of 0.1 microg/ml. Like bleomycin, complex R exerted its clastogenic effects without the need for metabolic activation and induced CAs of all types in lymphocytes treated in the G(2) and late S phases and, therefore, can be considered a radiomimetic. In addition, it induced more total CAs of chromatid-type than of chromosome-type. The reduction in the frequencies of CAs following the 20 h treatment as compared with those induced following the 3 h treatments indicated that human lymphocytes in the presence of complex R can partially tolerate the lesions involved in CA production. Based on the biological effects of complex R and the similarities between its functional group and that of bleomycin, possible mechanisms for complex R genotoxicity are discussed.     

Sonographic diagnosis of ureteral tumors.

We present our experience with transabdominal ultrasonographic diagnosis of ureteral tumors. During the years 1989 to 1998, 16 patients were diagnosed as having ureteral tumors. These patients were referred for sonographic examination for evaluation of hematuria (seven patients) or flank pain (four patients) or for follow-up screening in patients who were asymptomatic but at high risk for transitional cell carcinoma because of known past bladder tumor (five patients). Ten of these patients underwent intravenous urography examination, three patients had retrograde pyelography, and 11 patients underwent CT scanning. Ultrasonography revealed the ureteral tumors in all 16 patients, which appeared as hypoechoic intraluminal soft tissue. Three tumors were localized in the upper ureter, four in the middle ureter, and nine in the distal ureter. The degree of ureterohydronephrosis was minimal (two cases), mild (five cases), moderate (eight cases), or severe (one case). Eleven tumors caused local widening of the ureteral diameter. On intravenous urography, four patients had a nonfunctioning kidney, three patients had unexplained ureterohydronephrosis, and three patients showed ureteral filling defects, of which only two had irregular contours. On retrograde pyelography, two patients had filling defects (one of which with smooth margins), and one had a truncated ureter. On CT the tumor was clearly demonstrated in only seven patients. We found that ultrasonography can be a useful diagnostic tool in the workup of ureteral tumors.     

Ultrasound vs CT for the detection of ureteric stones in patients with renal colic.

The aim of our study was to compare the accuracy of non-contrast spiral CT with ultrasound (US) for the diagnosis of ureteral calculi in the evaluation of patients with acute flank pain. 62 consecutive patients with flank pain were examined with both CT and US over a period of 9 months. All patients were prospectively defined as either positive or negative for ureterolithiasis, based on follow-up evaluation. 43 of the 62 patients were confirmed as having ureteral calculi based on stone recovery or urological interventions. US showed 93% sensitivity and 95% specificity in the diagnosis of ureterolithiasis; CT showed 91% and 95%, respectively. Pathology unrelated to urinary stone disease was demonstrated in six patients. Although both modalities were excellent for detecting ureteral stones, consideration of cost and radiation lead us to suggest that US be employed first and CT be reserved for when US is unavailable or non-diagnostic.