Role of Ang1 and its interaction with VEGF-A in astrocytomas

Angiopoietins (Ang1 and Ang2) modulate the activity of the endothelial cell (EC)-specific receptor tyrosine kinase Tie2, which together with vascular endothelial growth factor (VEGF-A) and its EC-specific receptors, VEGFR1 and VEGFR2, regulate normal physiological vessel development. The functional role of angiopoietins in tumor angiogenesis, in particular astrocytoma angiogenesis, remains unclear. In this study, we focus on the specific contribution of Ang1 to the vascular growth of glioblastoma multiforme (GBM) and its interactive role with VEGF-A. Subcutaneous and intracranial GBM xenografts were generated using 3 established astrocytoma cell lines (U87, U373, and U343) that were transfected to stably over-express Ang1. GBM xenografts were also generated to express low levels of VEGF-A and high Angl. We found that Ang1 increases the vascular growth of both subcutaneous and intracranial xenografts of GBM by approximately 3-fold. However, the increased vascular growth was only seen in xenografts with concurrent VEGF-A elevation, since decreasing VEGF-A expression resulted in a loss of the pro-angiogenic growth advantage seen with Ang1. Collectively, our data suggest that Ang1 regulates GBM vascularity in a VEGF-A dependent manner, synergizing the initial pro-angiogenic response that is triggered by VEGF-A and promoting the vascular growth of GBM.     

Impact of serum creatinine measurement error on dose adjustment in renal failure

BACKGROUND: Doses of renally eliminated drugs should be adjusted according to kidney function to prevent adverse drug events and cost. Dose adjustment can be based on serum creatinine level, subsequent creatinine clearance estimation, and dosage calculation with consideration of the renal elimination properties of the respective compound. OBJECTIVE: Our objective was to quantify the impact and relevance of serum creatinine measurement error on dose adjustment in renal failure. METHODS: We analyzed 27914 measurements from external quality assessment surveys of 1878 German laboratories that used a kinetic alkaline picrate (69% of results) or an enzymatic method (25%) for creatinine determination. Linear models were fit for both methods combined and separately. On the basis of 95% confidence intervals (CIs) for creatinine values, 95% CIs for drug dosing were calculated. RESULTS: The 95% CI for a measured serum creatinine value was 0.80. Measured value < Reference method value < 1.28. Measured value for the kinetic alkaline picrate method and 0.87. Measured value < Reference method value < 1.21. Measured value for the enzymatic method. Applied to a data set of 6.5 million simulated patients with all possible combinations of characteristics relevant for drug dosing, the dosing error caused by serum creatinine measurement error did not exceed 25% in patients with creatinine clearance estimates lower than 50 mL/min according to the Cockcroft-Gault equation. For drugs completely eliminated by the kidneys in active form, the dosing error was up to 6-fold smaller than that which would occur if doses were not adjusted. CONCLUSION: The serum creatinine measurement error of current laboratory methods is small and is comparable to other errors influencing dose adjustment.     

A genealogical assessment of heritable predisposition to aneurysms

OBJECT: This study was conducted to investigate the familial and genetic contribution to intracranial, abdominal aortic, and all other types of aneurysms, and to define familial relationships among patients who present with the different aneurysm types. METHODS: The authors used a unique Utah resource to perform population-based analysis of the familial nature of aneurysms. The Utah Population Data Base is a genealogy of the Utah population dating back eight generations, which is combined with death certificate data for the state of Utah dating back to 1904. Taking into account the genetic relationships among all aneurysm cases derived from this resource, the authors used a previously published method to estimate the familiality of different aneurysm types. Using internal, birth-cohort-specific rates of disease calculated from the database, they estimated relative risks by comparing observed to expected rates of aneurysm incidence in defined sets of relatives of probands. CONCLUSIONS: Each of the three aneurysm types investigated showed significant evidence for a genetic component. Relatives of patients with intracranial aneurysms do not appear to be at increased risk for abdominal or other lesions, but relatives of patients with abdominal aortic aneurysms appear to be at increased risk for other types of these lesions.     

Balloon dilatation of anastomotic strictures secondary to surgical repair of oesophageal atresia

The purpose of this study was to evaluate the efficiency and safety of oesophageal balloon dilatation in strictures secondary to surgical treatment of oesophageal atresia in 25 children. Patients comprised 15 males and 10 females, aged 1-36 months. Median age was 4 months (interquartile range (IQR)=19). The strictures were more than 50% of oesophageal lumen and the delay from surgical treatment to balloon dilatation varied from 1 month to 36 months. Associated gastroesophageal reflux was noted in 15 patients. All procedures were performed under sedation using fluoroscopic guidance. Balloons of increasing diameter, 4-20 mm were used. Water soluble contrast swallow was performed after each dilatation session. A total of 115 balloon dilatation sessions were performed with a range of 1-14 procedures per patient (median 4 dilatations, IQR=4.5). Dilatation relieved the stricture in all patients over a follow-up period varying from 4 months to 33 months. The best results were noted in children under 6 months, who needed two or few dilatation sessions, with relative risk (RR) of 0.52 and 95% confidence interval of 0.29-0.92. The presence of associated gastroesophageal reflux indicated a high risk (RR of 12, p<0.001) for undergoing more than two balloon dilatation sessions. The only serious complications observed were two cases of oesophageal perforation, which were treated conservatively. Fluoroscopically guided balloon dilatation is a safe and effective treatment in the management of strictures secondary to surgical repair of oesophageal atresia, especially when started early (within 6 months of surgery) and not associated with gastroesophageal reflux.     

Intra-abdominal desmoplastic small round cell tumor in childhood: case report and review of the literature

Desmoplastic small round cell tumor (DSRCT) correspond to a recent clinicopathological entity, individualized in 1989 into the group of tumors with small round cells. This pathology puts ethiopathogenic, diagnostic, therapeutic and prognosis problems. Indeed, the ethiopathogenic is still unknown, diagnosis is asserted only by immuno-histochimic and cytogenetic study because of the big number of differential diagnoses and the anatomopathologic polymorphism. Its treatment is not well codified and its outcome remains dark in spite of therapeutic progress. The objective of this work is to report a personal observation of a DSRCT and to proceed to a review of the literature to clarify the epidemiological, clinical, paraclinical and therapeutic aspects of this rare tumor.     

Selegiline in the treatment of Parkinson's disease: its impact on orthostatic hypotension

Less than a consensus exists as to whether chronic treatment with selegiline in combination with levodopa/carbidopa in patients with Parkinson's disease, is associated with more pronounced orthostatic hypotension than treatment with levodopa/carbidopa alone. To resolve this issue, we compared orthostatic tolerance and autonomic reflexes in 95 patients with Parkinson's disease treated chronically with either selegiline alone (n = 10), levodopa/carbidopa alone (n = 49) or both agents combined (n = 36). Supine heart rate and blood pressure, autonomic cardiovascular reflexes and the frequency and magnitude of orthostatic hypotension were similar in all three treatment groups.     

Keratoprosthesis: preoperative prognostic categories

PURPOSE: Recent advances aimed at preventing and treating complications after keratoprosthesis surgery have improved prognosis, but it has been suspected that various preoperative diagnoses may carry substantially different postoperative outcomes. This article attempts to clarify the ranking of prognostic categories for patients undergoing keratoprosthesis surgery. METHODS: A retrospective review of the outcome in a recent series of 63 patient eyes operated at the Massachusetts Eye and Ear Infirmary between 1990 and 1997 and followed up for a minimum of 21 months. Anatomic retention of the device and the loss of vision caused by complications were recorded. The patients were divided into four categories according to preoperative cause. RESULTS: Anatomically, one keratoprosthesis extruded spontaneously. Another 10 were permanently removed because of complications. Of the 63 eyes, 10 never achieved a visual acuity of at least 20/200 vision because of preexisting retinal or optic nerve damage. The remaining 53 had a visual acuity of 20/200 to 20/20 as follows: Stevens-Johnson syndrome (n = 7), after 2 years: 33%, after 5 years: 0%; chemical burn (n = 17), after 2 years: 64%, after 5 years: 25%; ocular cicatricial pemphigoid (n = 20), after 2 years: 72%, after 5 years: 43%; graft failure in noncicatrizing conditions (dystrophies, degenerations, or bacterial or viral infections) when a repeat graft was expected to have a poor prognosis (n = 19), after 2 years: 83%, after 5 years: 68%. The difference in outcome between the Stevens-Johnson syndrome outcome group and the graft failure group or the ocular cicatricial pemphigoid group was statistically significant. In the group of 53 eyes, visual acuity was restored to 20/200 to 20/20 for a cumulative total of 138 years. CONCLUSION: Outcome of the keratoprosthesis surgery varied markedly with preoperative diagnosis. Most favorable was graft failures in non-cicatrizing conditions, whereas Stevens-Johnson syndrome was the worst. Ocular cicatricial pemphigoid and chemical burns occupied a middle ground. The difference between the groups seemed to correlate with the degree of past preoperative inflammation.