Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality

A total of 963 skeletons (408 Whites and 555 Blacks) from the Terry Collection were studied to examine macroscopic cranial methods of age estimation. The methods of Acsádi and Nemeskéri, Masset, Baker and Meindl and Lovejoy were applied to every skull. The results indicate that the most accurate techniques in this application were those that consider endocranial suture closure. The methods of Acsádi and Nemeskéri and Masset were the most accurate in all the subsamples (by population, sex, sex within population and in total), although the relative accuracy could vary in application to other populations.     

Clinical and biochemical phenotype in 11 patients with mevalonic aciduria

OBJECTIVE: Mevalonic aciduria is a consequence of the deficiency of mevalonate kinase, the first enzyme after 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the biosynthesis of cholesterol and nonsterol isoprenes. To establish the clinical and biochemical phenotype of mevalonic aciduria, the authors assembled their experience with 11 patients including attempts at therapeutic interventions. METHODS: Mevalonic acid in body fluids was determined by stable isotope dilution gas chromatography/mass spectroscopy with selected ion monitoring, ubiquinone-10 concentrations by reversed-phase high-pressure liquid chromatography. RESULTS: Varying degrees of severity of clinical illness were observed despite uniform, virtual absence of residual activity of the enzyme. The most severely affected patients have had profound developmental delay, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, and anemia, as well as diarrhea and malabsorption, and have died in infancy. Less severely affected patients have had psychomotor retardation, hypotonia, myopathy, and ataxia. All patients have had recurrent crises in which there was fever, lymphadenopathy, increase in size of liver and spleen, arthralgia, edema, and a morbilliform rash. Neuroimaging studies revealed selective and progressive atrophy of the cerebellum. Mevalonic acid concentrations were found to be grossly elevated in body fluids of all patients. Concentrations of plasma cholesterol were normal or only slightly reduced. Concentrations of ubiquinone-10 in plasma were found to be decreased in most patients. Abnormalities such as hypoglycemia, metabolic acidosis, or lactic acidemia, the usual concomitants of disorders of organic acid metabolism, were conspicuously absent. CONCLUSIONS: These observations establish the broad range of clinical symptoms and biochemical findings in mevalonic aciduria. It is concluded that although patients with mevalonic aciduria have a recognizable phenotype of serious clinical manifestations, some patients are likely to remain undiagnosed and may be found in a variety of subspecialty clinics, including neurology, gastroenterology, cardiology, and genetics.     

Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft

BACKGROUND: The plant cytotoxin saporin (SAP) is a potent ribosome-inactivating protein. When conjugated to basic fibroblast growth factor (FGF2), it selectively kills proliferating cells that have upregulated FGF receptors. In this study, we evaluated the effect of the recombinant chimeric mitotoxin rFGF2-SAP on venous anastomotic intimal hyperplasia, a major cause of failure of arteriovenous (AV) grafts. METHODS AND RESULTS: Recently designed expanded polytet-rafluoroethylene-based local infusion devices were implanted bilaterally as femoral AV conduits in six dogs. The venous anastomoses were the sites of continuous delivery of rFGF2-SAP (2.7 micrograms.kg-1.d-1) to one side and vehicle (4.6 microL.kg-1.d-1) as control to the contralateral side for 14 days. All animals survived, and all grafts were patent. Liver enzyme levels and histological analyses of liver, kidneys, and brain were normal, indicating the absence of systemic toxicity. Morphometric measurements and measurements of cell proliferation by bromodeoxyuridine index analysis were performed at both arterial and venous anastomoses. There were no significant differences between the treated grafts and the control grafts in intimal hyperplasia and intimal cell proliferation at the arterial anastomoses. In contrast, rFGF2-SAP reduced intimal thickness by 32%, intimal area by 40%, and cell proliferation index by 33% at the treated venous anastomoses compared with the control venous anastomoses (P < .05). CONCLUSIONS: These data demonstrate that local infusion of rFGF2-SAP significantly reduces venous anastomotic intimal hyperplasia and cell proliferation without systemic toxicity. This study suggests a new strategy for reducing intimal hyperplasia by the selective killing of proliferating smooth muscle cells with a potent chimeric mitotoxin through a novel local infusion device.     

Comparison of the retrograde and transseptal methods for ablation of left free wall accessory pathways

OBJECTIVES: The purpose of this study was to compare success rates, procedure and fluoroscopy times and complications for the transseptal and retrograde aortic approaches in a consecutive series of patients undergoing catheter ablation of left free wall accessory pathways. BACKGROUND: Radiofrequency catheter ablation of left-sided accessory pathways can be performed either by a retrograde, transaortic approach or by means of a transseptal puncture. METHODS: A total of 106 patients (mean age 33 years, range 4 to 79) underwent attempted catheter ablation of a single left-sided accessory pathway by either the retrograde or the transseptal approach, or both. In the first 65 patients, the retrograde aortic approach was the preferred initial method. In the most recent 51 patients, we first attempted the transseptal approach whenever a physician trained in the technique was available. Ultimately, 102 (96.2%) of 106 patients had successful ablation. RESULTS: Of 89 retrograde procedures, 85% resulted in elimination of accessory pathway conduction. Four retrograde procedures performed after failure of the transseptal approach were successful. Of the 13 patients with a failed retrograde procedure, 11 later underwent ablation using the transseptal approach. Twenty-six (85%) of 33 transseptal procedures were successful. All four patients with unsuccessful initial transseptal attempts were successfully treated with the retrograde method during the same session in the electrophysiology laboratory. Ten of 11 transseptal procedures after unsuccessful retrograde procedures were successful. Crossover from the retrograde to the transseptal approach was performed during a separate session in 9 of these 11. There was no difference in total procedure time (220 +/- 12.8 vs. 205 +/- 12.5 min) (mean +/- SEM) or fluoroscopy time (44.1 +/- 4.4 vs. 44.7 +/- 5.1 min) between the retrograde and transseptal methods. Ablation time was longer for the retrograde method (69.2 +/- 10.5 vs. 43.4 +/- 9.3 min) (p < 0.01). Of patients > or = 65 or < or = 16 years old, technical factors requiring crossover to the other technique or complications occurred in 7 (42%) of 17 patients undergoing the retrograde and 1 (11%) of 9 patients undergoing the transseptal approach (p < 0.01). The overall rate of complications was the same for both (6.7% for retrograde and 6.1% for transseptal). The most serious complication involved dissection of the left coronary artery with myocardial infarction during a retrograde procedure. CONCLUSIONS: The retrograde and transseptal approaches are complementary; if one method fails, the other should be attempted, yielding an overall success rate close to 100%. Because patients undergo heparinization immediately after the arterial system is entered during a retrograde procedure, failure of that approach requires crossover to the transseptal method during a separate session or reversal of heparin; if the transseptal method is tried first, crossover to the retrograde approach can be accomplished easily during the same session. To avoid complications related to access, the transseptal method should be the first used in children, the elderly and those with arterial disease or hypertrophic ventricles.     

Characterization of hepatic neoplasms: contribution of magnetic resonance

The reliability of MR imaging in the diagnosis and characterization of space occupying lesions affecting the liver are discussed in this study. We discuss the role of MR imaging in the diagnosis of these tumours and its advantages compared with other available techniques such as ultrasonography and CT. We also discuss the results of MR in the characterization of focal neoplastic masses.