Decision making and results in subtotal and total lower leg amputations: Reconstruction versus amputation

As a result of modern therapeutic and technological advances, the surgeon has the ability to salvage even the most severely injured lower limbs. However, the success of replantation nowadays is no longer measured simply on the basis of restoration of viability but also on functional outcome compared with primary amputation with early prosthetic fitting, the risk to the patient during and after replantation and the overall time of treatment which should not exceed 2 years. Although every major limb replantation has to be considered individually, the decision-making process for reconstruction (replantation/revascularisation) versus amputation with subsequent early prosthetic fitting should be determined by objective criteria. Based on personal experience and an extensive literature search, an algorithm for treatment of amputation or amputation-like injuries to the lower leg has been developed and tested in a clinical study. A 100% viability success rate was achieved. There was not only a significant increase in the percentage of “functional extremities” but also a doubling in grade I results. Moreover, there was a 50% reduction in patients presenting a “non-functional extremity”, and no patient required a secondary re-amputation. The replantation risk (e.g., risk of severe systemic disturbance during and/or after replantation) was about 16.6% (2/12) in our study. There was a significant decrease in the postoperative complication rate and no patient died during or after replantation. Based on our experience, if reconstruction in subtotal or total lower leg amputation is done for a well-selected patient group, good functional results with a reasonable replantation risk and a reasonable time for social re-integration can be achieved. © 1995 Wiley-Liss, Inc.     

The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.     

Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort.

High circulating concentration of insulin-like growth factor-I (IGF-I) and low circulating concentration of IGF binding protein-3 (IGFBP-3) have been associated with increased risk for breast, prostate, and colorectal cancers. Building on previous work in the Multiethnic Cohort (MEC) showing significant differences in IGF-I levels across racial/ethnic groups, we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a random sample of 1,000 MEC participants, which included Native Hawaiian, African American, Japanese, Latino, and White men and women. Crude analyses confirmed the existence of differences in protein levels with race/ethnicity, sex, age, and body size. Reproductive, physical activity, smoking, and diet variables had less consistent effects. In multivariate analyses, IGF-I levels were lower and IGFBP-3 were higher in females versus males. IGF-I and IGFBP-3 declined with increasing age in both genders. Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels; in men, height was significantly positively associated with both proteins. In women, alcohol was directly associated with IGFBP-3. Both proteins were lowest among female Latinos. IGF-I was highest among female African Americans. In men, IGFBP-3 was lowest among African Americans. Overall, although these factors were statistically significant determinants of IGF-related protein levels, they did not explain much of the variation in these levels. A positive correlation was found between IGF-I levels (ng/mL) and colon cancer incidence rates (per 100,000) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer.     

Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles

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Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

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