Modified cruciate incision for transabdominal radical nephrectomy

Experience with multiple organ harvesting procedures as well as orthotopic liver transplantation has provided for excellent extensive upper abdominal surgical exposure. We report use of a modified cruciate incision for transabdominal radical nephrectomy.     

Preparation and characterization of poly(styrene) microcapsules containing corrosion inhibitors

A technique has been developed to view cross-sections of microcapsules prepared by a multiple emulsion method. Poly(styrene) microcapsules were prepared by emulsifying an aqueous solution containing sodium dichromate, a corrosion inhibitor, into an organic solution containing dissolved poly(styrene). This water-in-oil emulsion was added to an aqueous solution with stirring to form a water-in-oil-in-water emulsion. The organic solvent was removed under reduced pressure resulting in polystyrene walled microcapsules containing aqueous sodium dichromate. The microcapsules were embedded in an agarose gel and sliced for examination by transmission electron microscopy. The cross-sections clearly identified a core surrounded by a sponge-like polymeric wall. The microcapsules were also examined by scanning electron microscopy. These photomicrographs showed a smooth, continuous external wall structure.     

Influence of a deficiency of the second component of complement on the bactericidal activity of neutrophils in vitro.

Serum from three patients with a complete, selective deficiency of the second component of complement (C2) did not promote optimal killing of Staphylococcus aureus, 502A by neutrophilic polymorphonuclear leukocytes (PMN) in vitro. The addition of C2 reagent or the presence of heat-stable opsonin in the C2-deficient serum corrected the defective killing of S. aureus that was observed with patient or control PMN. PMN from the patients or control subjects killed bacteria with equal efficiency under conditions of optimal opsonization (normal pooled serum). However, twice-washed control PMN were better than patient PMN in killing S. aureus under circumstances of suboptimal opsonization (C2-deficient serum, heated C2-deficient serum, heated normal pooled serum, or no replacement of serum). The latter finding was due to residual C2 on the surface of twice-washed control cells. As repeated washing of control PMN progressively removed cell-associated C2, the staphylocidal effectiveness of the control RMN decreased to the level of patient PMN. In contrast to the findings with S. aureus, triply-washed PMN from patients or controls killed normal numbers of Escherichia coli, ON2, in C2-deficient serum.     

Red cell deformability and lipid composition in two forms of acanthocytosis: enrichment of acanthocytic populations by density gradient centrifugation

Whole cell deformability and lipid determinations were performed on red cells from two patients who had acanthocytes in the peripheral blood (10% and 20% to 30%) and normal serum lipoprotein levels. One patient had typical chorea-acanthocytosis and the other had no clinical abnormalities associated with acanthocytosis. Red cells from the patient with chorea-acanthocytosis showed reduced deformability, as measured by a visco-diffractometric method (ektacytometry), which could be explained by the presence of increased numbers of dehydrated cells containing high concentrations of hemoglobin. The total cell population showed a modest increase in potassium efflux, which may be responsible for reduced cation content and dehydration in a subpopulation of cells. When the patients' red cells were separated into different density populations by centrifugation on density gradients, the cells of classic acanthocyte morphology were concentrated in the high-density layers. This was true for both patients, although the subject with acanthocytes and no clinical disorder had a normal red cell density distribution. Lipid analysis of both types of acanthocytes showed an increase in the relative proportion of sphingomyelin with respect to the glycerophospholipids. Total cholesterol and phospholipid levels were reduced in the chorea-acanthocytosis red cells, but the other acanthocytes did not differ significantly in total lipid content from normal control samples. Thus, the one common abnormal feature in these two forms of acanthocytosis is the increase in the proportion of red cell sphingomyelin. Because this is a very stable, immobile component of the membrane, we suggest that its relative enrichment could result from a defect in the transport and maintenance of glycerophospholipids. Further study of the dynamics of glycerophospholipid organization in acanthocytes may be useful in increasing our understanding of the genesis of abnormal, acanthocytic morphology.     

Enhanced hematopoietic activity of a human granulocyte/macrophage colony-stimulating factor-interleukin 3 fusion protein.

Granulocyte/macrophage colony-stimulating factor-interleukin 3 (GM-CSF-IL-3) fusion proteins were generated by construction of a plasmid in which the coding regions of human GM-CSF and IL-3 cDNAs were connected by a synthetic linker sequence followed by subsequent expression in yeast. Both GM-CSF-IL-3 and IL-3-GM-CSF fusion proteins were purified to homogeneity and shown to bind to cell-surface receptors through either their GM-CSF or IL-3 domains. The fusion proteins exhibited enhanced receptor affinity, proliferative activity, and hematopoietic colony-stimulating activity compared with either IL-3 and/or GM-CSF alone. This suggests that GM-CSF-IL-3 fusion proteins may hold future promise as therapeutic agents.     

Effect of Time to Titration to Maximum Dose of Statins on Cardiovascular Outcomes

Background

Recent trials have shown that high-dose HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular events in high-risk subjects within weeks of initiating therapy. We investigated the effect of time to titration to maximum dose of statin therapy on cardiovascular events.

Methods

From a list of all patients actively taking simvastatin 80 mg/day as of April 2003 at our hospital, two clinical pharmacists reviewed 213 electronic medical records including pharmacy records from November 1992 to April 2003. Data on cardiovascular risk factors, laboratory results, titration schedules, and outcomes were extracted from the electronic database. Titration period time frames were compared between patient groups using a Student t-test and multiple-variable logistic regression to account for other risk factors.

Results

Titration schedules and time frames to attain a regimen of simvastatin 80 mg/day were available for 154 (73%) subjects. Titrations ranged from 1 to 8 and averaged 2.3± 1.3 titrations per patient (median titrations = 2) over 1 month to 8.4 years. On follow-up, 47 patients experienced 80 cardiovascular-related outcomes. The average time to titration to maximum dose of statin therapy was longer for patients who experienced a cardiac event than for those who did not (3.5 ± 2.2 vs 2.1 ± 1.8 years; p = 0.0004). After accounting for other risk factors, the titration period was still significantly related to the presence of a cardiac event (p = 0.0060, odds ratio per month increase in the titration period 1.3, 95% CI 1.08, 1.58).

Conclusions

Despite potential limitations, the results of our study show that an excessive delay in titrating statin therapy to the optimal dose may lead to an increased risk of atherosclerosis-related events in high-risk patients.     

Mast cells are an essential hematopoietic component for polyp development

It is generally agreed that most colon cancers develop from adenomatous polyps, and it is this fact on which screening strategies are based. Although there is overwhelming evidence to link intrinsic genetic lesions with the formation of these preneoplastic lesions, recent data suggest that the tumor stromal environment also plays an essential role in this disease. In particular, it has been suggested that CD34(+) immature myeloid precursor cells are required for tumor development and invasion. Here we have used mice conditional for the stabilization of beta-catenin or defective for the adenomatous polyposis coli (APC) gene to reinvestigated the identity and importance of tumor-infiltrating hematopoietic cells in polyposis. We show that, from the onset, polyps are infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion of MC either pharmacologically or through the generation of chimeric mice with genetic lesions in MC development leads to a profound remission of existing polyps. Our data suggest that MC are an essential hematopoietic component for preneoplastic polyp development and are a novel target for therapeutic intervention.