The role of L-carnitine on a restricted number of myeloid leukemia progenitor cells: generation of atypical cell types.

AIM: Since cellular maturation largely depends on lipid metabolism, we examined whether L-carnitine (L-C), a substance involved in these biochemical pathways, is able to promote differentiation of the promyelocytic cell line HL-60. METHODS: Differentiation was assessed by marker analysis, morphology, immunohistochemistry, proliferation and cellular activity assays. RESULTS: L-C increases HLA-DR and CD14 surface antigens, while morphologic and marker analysis of the treated cells reveals the presence of monocytes, neutrophiles and few dendritic cells. What is important, however, is the induction of cells that have an atypical to this pathway allure staining positive for the neurofilament 3A10 monoclonal antibody, specific for nerve cells and the anti-p75 (Nerve Growth Factor Receptor) monoclonal antibody. The events described concern active and, at the same time, not proliferative senescent cells. CONCLUSIONS: L-C exerts its differentiation action on a certain fraction of the leukemic population yielding a non-negligible number of atypical for the myeloid lineage cells. These findings complement earlier and recent reports that describe the generation of cells of a different lineage irrelevant to their parent line of differentiation indicating that the hemopoietic pool appears to be the source of any kind of cell types according to the stimulus provided. Thus, in the context of the plasticity theory it appears that the HL-60 cell line also possess the potential to differentiate towards unexpected pathways.

Choices and goals in the treatment of the diabetic hypertensive patient.

The number of people living in the United States who have diabetes and high blood pressure is over 11 million and rising. Together, these two diseases are devastating to the whole body if not aggressively controlled. The tight recommendations put forth by the Joint National Committee VI for better control of blood pressure and control of proteinuria have helped diminish further organ failure in patients with hypertension and diabetes. Combination therapy has been found to be very effective, and one arm should be an angiotensin converting enzyme inhibitor.

Evolution of drugs that preserve renal function.

Over the past 50 years, many advances have been made in slowing the progression of renal disease from various causes. These advances have been primarily linked to defining new lower levels for blood pressure goals as well as understanding the importance of proteinuria reduction. To achieve these goals, it is also appreciated that agents that lower blood pressure must also lower proteinuria. This is not true for all antihypertensive drug classes--notably, direct-acting vasodilators, alpha-blockers, and dihydropyridine calcium antagonists. Interestingly, antihypertensive agents that also reduce proteinuria have been associated with cardiovascular risk reduction. Moreover, an understanding of combinations of antihypertensive medications that provide additive reductions in proteinuria may be even more efficacious for slowing renal disease progression. It is hoped that these advances and the projected advances in pharmacogenetics will reduce the current increasing incidence of people going on dialysis.

Further experience with transcatheter closure of the patent ductus arteriosus using the Amplatzer duct occluder.

OBJECTIVE: The aim of this study was to report further experience with transcatheter closure of the patent ductus arteriosus (PDA) using the Amplatzer duct occluder (ADO). BACKGROUND: The design of previously used devices is not ideal for this purpose, and their use has been associated with several drawbacks, especially in large PDAs. METHODS: Forty-three patients, aged 0.3 to 33 years (mean 6.4+/-6.7 years), with a moderate to large, type A to E PDA, underwent attempted transcatheter closure using the ADO. The device is a plug-shaped repositionable occluder made of 0.004-in. nitinol wire mesh. It is delivered through a 5F to 6F long sheath. The mean PDA diameter (at the pulmonary end) was 3.9+/-1.2 mm (range 2.2 to 8 mm). All patients had color flow echocardiographic follow-up (6 to 24 months) at 24 h, 1 and 3 months after closure, and at 6-month intervals thereafter. RESULTS: The mean ADO diameter was 6.1+/-1.4 mm (range 4 to 10 mm). Complete angiographic closure was seen in 40 of 43 patients (93%; 95% confidence interval [CI] 85.4% to 100%). The remaining three patients had a trivial angiographic shunt through the ADO. At 24 h, color flow mapping revealed no shunt in all patients. A 9F long sheath was required for repositioning of a misplaced 8-mm device into the pulmonary artery. The mean fluoroscopy time was 7.9+/-1.6 min (range 4.6 to 12 min). There were no complications. No obstruction of the descending aorta or the pulmonary artery branches was noted on Doppler follow-up studies. Neither thromboembolization nor hemolysis or device failure was encountered. CONCLUSIONS: Transcatheter closure using the ADO is an effective and safe therapy for the majority of patients with patency of the arterial duct. Further studies are required to establish long-term results in a larger patient population.